Pubmed abstracts for Protein-Protein Interaction search result :


Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.57956842
NEMO interacts with a COOH terminal sequence within both IKKs termed the NEMO binding domain ( NBD ) , and a cell permeable NBD peptide blocks NEMO / IKKbeta interactions and inhibits tumor necrosis factor alpha induced NF kappaB . 0.57956842^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
In contrast , IkappaB kinase gamma is recruited through the C terminal cytoplasmic region and this is essential for activation of NF kappaB . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
We hypothesized that caspase 1 may serve as a scaffolding molecule that promotes RIP 2 interaction with IkappaB kinase gamma thus inducing NF kappaB activation . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Polyubiquitination of IkappaB kinase gamma ( IKKgamma ) , indicative for enhanced NF kappaB activation , was increased in splenic lymphocytes and promoted the survival of B cells ex vivo . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
In the present study , the role of the NF kappaB signaling pathway in FasL gene expression was examined using a mutant T cell line deficient in an essential NF kappaB signaling component , IkappaB kinase gamma . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
The gene for NEMO ( NF kappaB essential modulator ) / IKKgamma ( IkappaB kinase gamma ) has been mapped to a position 200 kilobases proximal to the factor 8 locus . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Tax fails to induce apoptosis in T cells lacking IkappaB kinase gamma ( IKKgamma ) , an essential component of the NF kappaB signaling pathway . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
IkappaB kinase gamma ( IKKgamma ) ( also known as NEMO , Fip 3 , and IKKAP 1 ) is the essential regulatory component of the IKK complex ; it is required for NF kappaB activation by various stimuli , including tumor necrosis factor alpha ( TNF alpha ) , interleukin 1 ( IL 1 ) , phorbol esters , lipopolysaccharides , and double stranded RNA . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Tetrameric oligomerization of IkappaB kinase gamma ( IKKgamma ) is obligatory for IKK complex activity and NF kappaB activation . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
A role for NF kappaB essential modifier / IkappaB kinase gamma ( NEMO / IKKgamma ) ubiquitination in the activation of the IkappaB kinase complex by tumor necrosis factor alpha . ^^^ NEMO ( NF kappaB essential modifier ) / IKKgamma ( IkappaB kinase gamma ) is required for the activation of the IkappaB kinase complex ( IKK ) by inflammatory stimuli such as tumor necrosis factor ( TNF alpha ) . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
The zinc finger mutation C417R of 1 kappa B kinase gamma impairs lipopolysaccharide and TNF mediated NF kappa B activation through inhibiting phosphorylation of the 1 kappa B kinase beta activation loop . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Recent studies have identified the tumor suppressor CYLD , loss of which causes a benign human syndrome called cylindromatosis , as a key negative regulator for NF kappaB signaling by deubiquitinating tumor necrosis factor ( TNF ) receptor associated factor ( TRAF ) 2 , TRAF 6 , and NEMO ( NF kappaB essential modulator , also known as IkappaB kinase gamma ) . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Mutant versions of IKKAP 1 , which either lack the N terminal IKK 2 binding domain or contain only the IKK 2 binding domain , disrupt the NF kappaB signal transduction pathway . ^^^ IKKAP 1 therefore appears to mediate an essential step of the NF kappaB signal transduction cascade . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
This direct interaction with IKK gamma correlates with Tax induced IkappaB alpha phosphorylation and NF kappaB activation . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
In this report , we show that Tax physically interacts with a regulatory component of the IKK complex , the NF kappaB essential modulator or IKKgamma ( NEMO / IKKgamma ) . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
This study compared the effect of these stimuli on endogenous IkappaB kinase ( IKK ) signalsome activation and IkappaB phosphorylation / proteolysis in human monocytic cells and investigated the role of the signalsome proteins IKK alpha , IKK beta , NF kappaB inducing kinase ( NIK ) , IKK gamma ( NF kappaB essential modulator ) , and IKK complex associated protein . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Somatic mutagenesis studies of NF kappa B signaling in human T cells : evidence for an essential role of IKK gamma in NF kappa B activation by T cell costimulatory signals and HTLV 1 Tax protein . ^^^ Expression of exogenous IKK gamma in the mutant cells restored NF kappa B activation by both the T cell costimulation agents and Tax . ^^^ These findings provide genetic evidence for the requirement of IKK gamma in NF kappa B signaling triggered by both T cell costimulatory signals and HTLV 1 Tax protein . . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
There is strong biochemical and genetic evidence that the IKK complex , which consists of two catalytic subunits , IKK alpha and IKK beta , and a regulatory subunit , IKK gamma , is the master regulator of NF kappa B mediated innate immune and inflammatory responses . ^^^ In the absence of IKK gamma , which normally connects IKK to upstream activators , no IKK or NF kappa B activation can occur . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Severe liver degeneration and lack of NF kappaB activation in NEMO / IKKgamma deficient mice . ^^^ A novel , noncatalytic component of this kinase complex called NEMO ( NF kappaB essential modulator ) / IKKgamma was identified recently . ^^^ NEMO / IKKgamma deficient primary murine embryonic fibroblasts ( MEFs ) lack detectable NF kappaB DNA binding activity in response to TNFalpha , IL 1 , LPS , and Poly ( IC ) and do not show stimulus dependent IkappaB kinase activity , which correlates with a lack of phosphorylation and degradation of IkappaBalpha . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
A mutant form of IKKgamma deficient in binding to IKKalpha and IKKbeta inhibited NF kappaB activation induced by RICK or RIP . ^^^ Enforced oligomerization of RICK or RIP as well as of IKKgamma , IKKalpha , or IKKbeta was sufficient for induction of NF kappaB activation . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
IKKalpha and IKKbeta are two catalytic subunits of a core IKK complex that also contains the regulatory subunit NEMO ( NF kappaB essential modulator ) / IKKgamma . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Substitution of the C terminal region of IKKgamma , which interacts with RIP , with a truncated DR 4 lacking its cytoplasmic death domain , produced a molecule that could induce IKK and NF kappaB activation in cells in response to TRAIL . ^^^ Enforced oligomerization of the N terminus of IKKgamma or truncated IKKalpha or IKKbeta lacking their serine cluster domains can also induce IKK and NF kappaB activation . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Expression of exogenous IKKgamma in the mutant cells restored NF kappaB activation , thus confirming the essential role of this regulatory factor in IKK activation by the cellular and viral stimuli . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
The IkappaB kinase ( IKK ) complex , composed of two catalytic subunits ( IKKalpha and IKKbeta ) and a regulatory subunit ( IKKgamma ) , is the key enzyme in activation of nuclear factor kappaB ( NF kappaB ) . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
IKKgamma / NEMO is an essential regulatory component of the IkappaB kinase complex that is required for NF kappaB activation in response to various stimuli including tumor necrosis factor alpha and interleukin 1beta . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Disruption of NF kappa B signaling and chemokine gene activation by retroviral mediated expression of IKK gamma / NEMO mutants . ^^^ Overexpression of Delta C IKK gamma resulted in a reduction in IKK kinase activity in vitro , a subsequent decrease in NF kappa B DNA binding activity , and inhibition of chemokine gene induction in response to TNFalpha stimulation or paramyxovirus infection . ^^^ This study demonstrates the efficacy of Delta C IKK gamma as a repressor of IKK signaling and NF kappa B activation and suggests a potential gene therapy approach to limit chronic inflammation due to chemokine hyperactivation . . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
To further elucidate the mechanism involved in this phenomenon , we analyzed both the expression levels of upstream kinases ( IkappaB kinase ( IKK ) alpha , IKK beta , IKK gamma , and NF kappaB inducing kinase ( NIK ) ) and the IKK activity in cells . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Overexpression of either IKK gamma or IKAP blocked tumor necrosis factor alpha induction of an NF kappa B dependent reporter construct , but IKAP in addition affected several NF kappa B independent promoters . ^^^ Whereas specific down regulation of IKK gamma protein levels by antisense oligonucleotides significantly reduced cytokine mediated activation of the IKK complex and subsequent NF kappa B activation , a similar reduction of IKAP protein levels had no effect on NF kappa B signaling . ^^^ We conclude that while IKK gamma is a stoichiometric component of the IKK complex , obligatory for NF kappa B signaling , IKAP is not associated with IKKs and plays no specific role in cytokine induced NF kappa B activation . . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Activation of NF kappaB is critically dependent on serine phosphorylation of the IkappaB protein by the multi component IkappaB kinase ( IKK ) containing two catalytic subunits ( IKKalpha and IKKbeta ) and one regulatory subunit ( IKKgamma ) . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
The 1 kappa B kinase ( IKK ) , consisting of the IKK 1 and IKK 2 catalytic subunits and the NEMO ( also known as IKK gamma ) regulatory subunit , phosphorylates 1 kappa B proteins , targeting them for degradation and thus inducing activation of NF kappa B ( reviewed in refs 1 , 2 ) . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
A derivative of 70Z / 3 cells , 1 . 3E2 cells , are defective in NF kappaB activation due to the lack of the IkappaB kinase ( IKKgamma ) protein . ^^^ Ectopic expression of IKKgamma can rescue NF kappaB activation in response to lipopolysaccharides ( LPS ) and interleukin 1beta ( IL 1beta ) , but not to PMA . ^^^ Stable expression of either novel PKCtheta or delta but not classical PKCbetaII in 1 . 3E2 IKKgamma expressing cells rescues PMA activation of NF kappaB and JNK signaling , demonstrating a critical role of novel PKCs for B cell activation . . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Tumor necrosis factor ( TNF ) and phorbol ester induce TNF related apoptosis inducing ligand ( TRAIL ) under critical involvement of NF kappa B essential modulator ( NEMO ) / IKKgamma . ^^^ In cells deficient for NF kappaB essential modulator ( NEMO ) / IKKgamma , an essential component of the NF kappaB inducing 1 kappaB kinase ( IKK ) complex , induction of TRAIL expression was completely abrogated but was recovered in cells restored for IKKgamma expression . ^^^ As both TNF and PMA rapidly induce NF kappaB activation this suggests that NEMO / IKKgamma dependent activation of the NF kappaB pathway is necessary but not sufficient for up regulation of TRAIL in T cells . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Within the cascade of proteins whose activities impinge upon the activation of NF kappaB , the NEMO ( NF kappaB essential modulator ) / IKKgamma protein is required for the activation of the IkappaB kinases , which in turn , promote the degradation of IkappaB proteins , leading to the derepression of NF kappaB activity . ^^^ Courtois and Isral discuss the role of NEMO / IKKgamma in normal physiological activation of NF kappaB and the consequences of defective NF kappaB activation , as an effect of NEMO / IKKgamma mutations , which can lead to incontinentia pigmenti , a disease marked by alopecia , tooth eruption , skin lesions , and changes in skin pigmentation . . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Recent data indicate that the constitutive activation of the NF kappaB pathway by the human T cell lymphotrophic virus , type 1 , Tax protein leads to enhanced phosphorylation of IKKgamma / NEMO by IKKbeta . ^^^ IKKgamma / NEMO is rapidly phosphorylated following treatment of cells with stimuli such as tumor necrosis factor alpha and interleukin 1 that activate the NF kappaB pathway . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
NF kappaB essential modifier ( NEMO ) , also known as IKK gamma , is a member of the 1 kappaB kinase complex responsible for phosphorylating 1 kappaB , allowing the release and activation of NF kappaB . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
PKK mediated NF kappa B activation required IKK alpha and IKK beta but not IKK gamma , the regulatory subunit of the IKK complex . ^^^ These results suggest that PKK is a member of the RICK / RIP family of kinases , which is involved in a PKC activated NF kappa B signaling pathway that is independent of Bcl 10 and IKK gamma . . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
IKK is composed of a heterodimer of the catalytic IKK alpha and IKK beta subunits and a presumed regulatory protein termed NEMO ( NF kappa B essential modulator ) or IKK gamma . ^^^ Here we identify TANK ( TRAF family member associated NF kappa B activator ) as a NEMO / IKK gamma interacting protein via yeast two hybrid analyses . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Furthermore , deletion and point mutation analyses reveal that both the amino terminal IKK binding and the carboxy terminal putative zinc finger domains of NEMO ( IKK gamma ) are critical for UV induced NF kappa B activation . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
We have isolated a Jurkat T cell mutant that exhibits enhanced sensitivity to TNF induced apoptosis as a result of a deficiency in 1 kappaB kinase gamma ( IKKgamma ) / NEMO , an essential component of the IKK complex and NF kappaB pathway . ^^^ We show here that the zinc finger protein A 20 is an NF kappaB inducible gene that can protect the IKKgamma deficient cells from TNF induced apoptosis by disrupting the recruitment of the death domain signaling molecules TRADD and RIP to the receptor signaling complex . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
In Jurkat T cells deficient for 1 kappaB kinase gamma ( IKKgamma , also known as NEMO ) , an essential component of the NF kappaB inducing IKK complex , induction of TRAF 4 was completely inhibited . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Despite their interaction with IKK gamma , PP2A interaction defective Tax mutants failed to activate NF kappa B . ^^^ Our data support the notion that IKK gamma associated PP2A is responsible for the rapid deactivation of IKK , and inhibition of PP2A by Tax in the context of IKK 10 PP2A 10 Tax ternary complex leads to constitutive IKK and NF kappa B activation . . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Human T cell leukemia virus type 1 oncoprotein Tax activates NF kappaB through direct binding to IKK gamma , the regulatory component of the IkappaB kinase complex . ^^^ Taken together , our findings suggest a new model of Tax activation of NF kappaB , in which Tax interacts with IKK gamma to stimulate its oligomerization . . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
To analyse bovine IKKalpha ( IKK 1 ) , IKKbeta ( IKK 2 ) and IKKgamma ( or NF kappaB Essential MOdulator , NEMO ) and their substrate IkappaBalpha ( Inhibitor of NF kappaB ) , the corresponding cDNAs of these molecules were isolated , sequenced and characterized . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
These results show the importance of SLP 76 and PLCgamma 1 for NF kappaB activation and raft translocation of PKCtheta and IKKgamma . . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
The classical pathway involved the IkappaB kinase ( IKK ) beta and IKKgamma dependent degradation of IkappaBalpha and resulted in the rapid but transient activation of primarily RelA containing NF kappaB dimers . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Anhidrotic ( hypohidrotic ) ectodermal dysplasia associated with immunodeficiency ( EDA ID ; OMIM 300291 ) is a newly recognised primary immunodeficiency caused by mutations in NEMO , the gene encoding nuclear factor kappaB ( NF kappaB ) essential modulator , NEMO , or inhibitor of kappaB kinase ( IKK gamma ) . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Mutations in the 10 linked gene encoding IKKgamma can interfere with NF kappaB signaling and lead to immunodeficiency disease . ^^^ Although its precise mechanism of action remains unknown , IKKgamma is phosphorylated in concert with the induction of NF kappaB by the viral oncoprotein Tax and the proinflammatory cytokine tumor necrosis factor alpha ( TNF ) . ^^^ As such , IKKbeta mediated phosphorylation of IKKgamma at these specific serine targets may facilitate proper regulation of NF kappaB signaling in the immune system . . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
NF kappaB activity in mammalian cells is regulated through the IkappaB kinase ( IKK ) complex , consisting of two catalytic subunits ( IKKalpha and IKKbeta ) and a regulatory subunit ( IKKgamma ) . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Of note , TNF induced NF kappaB DNA binding activity and activation of IkappaB kinases ( IKKs ) were markedly impaired in FAK / cells , whereas the expression of TNF receptor 1 or other signaling molecules such as receptor interacting protein ( RIP ) , tumor necrosis factor receptor associated factor 2 ( TRAF 2 ) , IKKalpha , IKKbeta , and IKKgamma was unchanged . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
We used an 11 amino acid sequence NEMO binding domain ( NBD ) that selectively inhibits the IKKgamma ( NEMO ) / IKKbeta interaction , preventing NF kappaB activation . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Treatment with NEMO binding domain peptide , which prevents NF kappaB activation by selectively inhibiting IKKgamma interaction with IKK complex , also blocked the TNF alpha induced TRPC 1 expression . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Triggering TCR in mutant Jurkat T cells lacking IKKgamma / NEMO failed to induce IL 2 due to a selective loss in 1 kappaB kinase activity , 1 kappaBalpha degradation and NF kappaB DNA binding activity . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Epstein Barr virus encoded latent infection membrane protein 1 regulates the processing of p 100 NF kappaB 2 to p 52 via an IKKgamma / NEMO independent signalling pathway . ^^^ Interestingly , while the ability of LMP 1 to activate the canonical NF kappaB pathway is impaired in cells lacking IKKgamma / NEMO , the regulatory subunit of the IKK complex , p 100 processing remains unaffected . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Genetically , at least 4 distinct molecular defects have been identified that result in defective CSR and present as HIGM syndromes : defects of the CD 40 ligand gene ( CD40L ; HIGM 1 , 10 linked ) , the activation induced cytidine deaminase gene ( AID ; HIGM 2 , autosomal recessive ) , the CD 40 gene ( HIGM 3 , autosomal recessive ) , and the nuclear factor kappaB ( NF kappaB ) essential modulator gene ( NEMO , or IKK gamma , 10 linked ) . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Segregation of NF kappaB activation through NEMO / IKKgamma by Tax and TNFalpha : implications for stimulus specific interruption of oncogenic signaling . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Furthermore , we showed that these IKKbeta IKKgamma complexes are involved in mainstream NF kappaB activation cascades because they can be activated by tumor necrosis factor . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Finally , acetyltransferases and deacetylases interact directly with several proteins involved in the NF kappaB signaling pathway , including NF kappaB itself , IkappaBalpha , IKKalpha and IKKgamma . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
A dominant negative mutant of IKKgamma inhibited the FasL induced NF kappaB activation . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Two hundred kilobases proximal to this locus , the gene for NEMO ( NF kappaB essential modulator ) / IKKgamma ( 1 kappaB kinase gamma ) has been mapped . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
IKKgamma inhibits activation of NF kappaB by NIK . ^^^ IKKgamma is a component of the IKK complex , which regulates NF kappaB activity . ^^^ In a co transfection assay with a CAT reporter plasmid , NIK activated NF kappaB dependent gene expression approximately two fold and this expression was inhibited by co transfection of a wild type IKKgamma expression plasmid . ^^^ Inhibition by IKKgamma also occurred in an assay with a dominant negative mutant of NIK but not with a C terminal deletion mutant of IKKgamma , indicating that the C terminal 100 amino acids of IKKgamma are important for negative regulation of NF kappaB activation . ^^^ Our results suggest that overexpression of IKKgamma inhibits activation of NF kappaB by NIK by competing with NIK for interaction with IKKbeta . . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
We now use cells lacking expression of TRAF 2 , TRAF 5 , TRAF 6 , IKKalpha , IKKbeta , IKKgamma , TAB 2 , IL 1 receptor associated kinase ( IRAK ) 1 , or IRAK 4 to assess their roles in LMP 1 mediated NF kappaB activation . ^^^ More surprisingly , NF kappaB responses were near normal in TRAF 2 and TRAF 5 double KO MEFs , IKKgamma KO MEFs , TAB 2 KO MEFs , and IRAK 4 KO MEFs but were highly deficient in TRAF 6 KO MEFs and IRAK 1 KO HEK 293 cells . ^^^ These data extend a role for IKKalpha in IKKbeta regulation , identify an unusual IKKbeta dependent and IKKgamma independent NF kappaB activation , and indicate that IRAK 1 and TRAF 6 are essential for LMP 1 induced NF kappaB activation . . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
LTbetaR and CD 40 activation of p100 / NF kappaB 2 is now known to be NIK / IKKalpha dependent and IKKbeta / IKKgamma independent . ^^^ Thus , LMP 1 induces typical canonical IKKbeta / IKKgamma dependent , atypical canonical IKKbeta dependent / IKKgamma independent , and noncanonical NIK / IKKalpha dependent NF kappaB activations ; NIK / IKKalpha dependent NF kappaB activation is principally mediated by the LMP 1 TRAF binding site . . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Bcl 10 overexpression is sufficient to activate NF kappaB , a process that requires the NF kappaB essential modulator NEMO ( also known as IKK gamma ) , which is the regulatory subunit of the IkappaB kinase complex . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
The effects of age and CR on muscle mass , myocyte area , fiber number , myocyte TNF alpha expression , plasma TNF alpha levels , and specific elements linked with the TNF alpha signaling cascade ( TNF R 1 , IKKgamma , IkappaBalpha , p 65 , NF kappaB binding activity , FADD , caspase 8 , and DNA fragmentation ) were investigated in soleus ( predominately Type 1 fiber ) , and superficial vastus lateralis ( SVL , predominately Type 2 fiber ) , of 6 month old ad libitum fed ( 6AL ) , 26 month old ad libitum fed ( 26AL ) , and 26 month old calorie restricted ( 26CR ) male Fischer 344 rats ( CR = 40 % restriction compared with ad libitum ) . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
It was found that a treatment of 20 microg / ml emodin inhibited the expression of a panel of inflammatory associated genes , including TNFalpha , iNOS , IL 10 , cytosolic IkappaBalpha , IKK alpha and IKK gamma , to different extents as well as the nuclear translocation of NF kappaB ( nuclear factor kappaB ) . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
The alteration in NF kappaB DNA binding activity was neither accompanied by any change in the expression of the inhibitor kappaB ( IkappaB ) kinases , IKKalpha , IKKbeta , and IKKgamma nor in the expression of the NF kappaB inhibitor proteins , IkappaBalpha and IkappaBbeta . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Although activation of the NF kappaB pathway by Tax involves its interaction with the regulatory subunit of the IkappaB kinase ( IKK ) complex , NEMO / IKKgamma , the mechanism by which Tax activates specific cellular genes in the nucleus remains unknown . ^^^ Here , we demonstrate that the attachment of SUMO 1 to Tax regulates its localization in nuclear bodies and the recruitment of both the RelA subunit of NF kappaB and free IKKgamma in these nuclear structures . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Co expression of IkappaB alpha , IkappaB beta , IkappaB kinase ( IKK ) alpha , IKKbeta , IKKgamma , nuclear factor ( NF ) kappaB inducing kinase and tumour necrosis factor receptor associated factor 2 dominant negative constructs with LMP 1 inhibited the activation of the CCL 20 promoter by LMP 1 , suggesting that LMP 1 induces CCL 20 via NF kappaB signalling . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
An alternative splice product of IkappaB kinase ( IKKgamma ) , IKKgamma delta , differentially mediates cytokine and human T cell leukemia virus type 1 tax induced NF kappaB activation . ^^^ Because IKKgamma Delta protein is lacking a critical coiled coil domain important in protein protein interactions , we sought to determine its signaling properties by examining its ability to self associate , couple to activators of the canonical pathway , and mediate human T cell leukemia virus type 1 ( HTLV 1 ) Tax induced NF kappaB activity . ^^^ Similarly , IKKgamma delta mediates IKK kinase activity and downstream NF kappaB dependent transcription in response to tumor necrosis factor ( TNF ) and the NF kappaB inducing kinase IKKalpha signaling pathway . ^^^ Surprisingly , however , in contrast to IKKgamma WT , IKKgamma delta is not able to mediate HTLV 1 Tax induced NF kappaB dependent transcription , even though IKKgamma delta binds and colocalizes with Tax . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
FIP 3 , isolated as a type 2 adenovirus E 3 14 . 7 kDa interacting protein , is an essential component of the multimeric IkappaB alpha kinase ( IKK ) complex and has been shown to interact with various components ( Fas receptor interacting protein , NF kappaB inducing kinase , IKKbeta ) of the NF kappaB activation pathway . ^^^ FIP 3 has also been shown to repress basal and tumor necrosis factor ( TNF ) alpha induced NF kappaB activity as well as to induce cell death when overexpressed . ^^^ The NF kappaB inhibitory activity and the E 3 14 . 7K binding domains were mapped at the carboxyl half of the FIP 3 protein . ^^^ We also found that the carboxyl terminal half of FIP 3 blocked TNFalpha induced IkappaB alpha phosphorylation and subsequent degradation , which suggests that the stabilization of the cytoplasmic inhibitor of NF kappaB underlies the FIP 3 inhibition of NF kappaB activity . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Complementation cloning of NEMO , a component of the IkappaB kinase complex essential for NF kappaB activation . ^^^ The recovered full length cDNA encodes a 48 kDa protein , NEMO ( NF kappaB Essential MOdulator ) , which contains a putative leucine zipper motif . ^^^ The NEMO cDNA was also able to complement another NF kappaB unresponsive cell line , 1 . 3E2 , in which the protein is also absent , allowing us to demonstrate that this factor is required not only for Tax but also for LPS , PMA , and IL 1 stimulation of NF kappaB activity . . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Here , we demonstrate that the cytoplasmic NH 2 terminal procaspase 8 cleavage product of c FLIP ( p 22 FLIP ) found in nonapoptotic malignant cells , primary T and B cells , and mature dendritic cells ( DCs ) strongly induces nuclear factor kappaB ( NF kappaB ) activity by interacting with the IkappaB kinase ( IKK ) complex via the IKKgamma subunit . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Here , we report that AGRO 100 also associates with nuclear factor kappaB ( NF kappaB ) essential modulator ( NEMO ) , which is a regulatory subunit of the inhibitor of kappaB ( IkappaB ) kinase ( IKK ) complex , and also called IKKgamma . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Identification of a cell protein ( FIP 3 ) as a modulator of NF kappaB activity and as a target of an adenovirus inhibitor of tumor necrosis factor alpha induced apoptosis . ^^^ FIP 3 , which contains leucine zippers and a zinc finger domain , inhibits both basal and induced transcriptional activity of NF kappaB and causes a late appearing apoptosis with unique morphologic manifestations . ^^^ FIP 3 also was shown to bind to other cell proteins , RIP and NIK , which previously had been described as essential components of TNF alpha induced NF kappaB activation . ^^^ In addition , FIP 3 inhibited activation of NF kappaB induced by TNF alpha , the TNFR 1 receptor , RIP , NIK , and IKKbeta , as well as basal levels of endogenous NF kappaB in 293 cells . ^^^ Because the activation of NF kappaB has been shown to inhibit apoptosis , FIP 3 appears both to activate a cell death pathway and to inhibit an NF kappaB dependent survival mechanism . . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Isolation of full length cDNA and chromosomal localization of human NF kappaB modulator NEMO to Xq 28 . ^^^ Others have shown that expression of mouse NEMO can complement the lack of responsiveness to NF kappaB stimuli in two NEMO deficient cell lines . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Enforced expression of NEMO in cells revealed that NEMO can both promote and block NF kappaB activation and dramatically augments the phosphorylation of c Jun . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Phorbol esters and cytokines regulate the expression of the NEMO related protein , a molecule involved in a NF kappa B independent pathway . ^^^ Recently , we identified the NF kappaB Essential Modulator ( NEMO ) as an essential component of this pathway . ^^^ NEMO is a structural and regulatory subunit of the high molecular kinase complex ( IKK ) responsible for the phosphorylation of NF kappaB inhibitors . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Disruption of the 10 linked gene encoding NF kappa B essential modulator ( NEMO ) produces male embryonic lethality , completely blocks NF kappa B activation by proinflammatory cytokines , and interferes with the generation and / or persistence of lymphocytes . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Selective inhibition of NF kappaB activation by a peptide that blocks the interaction of NEMO with the IkappaB kinase complex . ^^^ Activation of NF kappaB requires the activity of an inhibitor of kappaB ( IkappaB ) kinase ( IKK ) complex containing two kinases ( IKKalpha and IKKbeta ) and the regulatory protein NEMO ( NF kappaB essential modifier ) . ^^^ A cell permeable NBD peptide blocked association of NEMO with the IKK complex and inhibited cytokine induced NF kappaB activation and NF kappaB dependent gene expression . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Functional analysis of the interleukin 1 receptor associated kinase ( IRAK 1 ) in interleukin 1 beta stimulated nuclear factor kappa B ( NF kappa B ) pathway activation : IRAK 1 associates with the NF kappa B essential modulator ( NEMO ) upon receptor stimulation . ^^^ Furthermore , we have demonstrated that endogenous IRAK 1 becomes phosphorylated upon IL 1 beta treatment and can be detected along with NF kappa B essential modulator ( NEMO ) and 1 kappa B kinase beta ( IKK beta ) in high molecular mass complexes of 600 800 kDa . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
In addition , inhibition of Tax mediated NF kappaB activation by coexpression of IkappaBalpha restored c Myb transcription , and Tax was unable to block c Myb transcription in a NEMO knockout cell line . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
IP is caused by mutations in a gene called NEMO , which encodes a regulatory component of the IkappaB kinase complex required to activate the NF kappaB pathway . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
IP results from mutations in the gene for NF kappaB essential modulator ( NEMO ) , with deletion of exons 4 10 of NEMO accounting for > 80 % of new mutations . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Recently it was shown that the causative mutation is located on the NEMO ( ' NF kappa B essential modulator ' ) gene . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
The IKK complex , containing two catalytic subunits IKKalpha and IKKbeta and a regulatory subunit NEMO , plays central roles in signal dependent activation of NF kappaB . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Until recently , most studies of the two pathways have solely focused on the core signaling complexes that are shared by the different receptors : death inducing complexes containing the cysteine proteases caspase 8 and caspase 10 , bound to the adapter protein MORT1 / FADD ( mediator of receptor induced toxicity / Fas associated DD protein ) , and the NF kappaB activating complex , composed of the protein kinases IKK 1 ( IkappaB kinase 1 ) and IKK 2 ( IkappaB kinase 2 ) and the regulatory subunit NEMO ( NF kappaB essential modulator ; the ' IKK signalosome ' ) . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Molecules important for NF kappaB and JNK / stress activated protein kinase activation such as IKKbeta , NEMO , MAP3K and TRAF 6 are discussed , as is the impact of BAFF and its receptors on B cell survival . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
We have also included NF kappaB essential modifier ( NEMO ) defects , which lead to 10 linked ectodermal dysplasia , with or without lymphedema and osteopetrosis , and a wide range of involvement of the immune system , which can mimic the hyper IgM phenotype . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Activation of NF kappaB is mediated by the IkappaB kinase ( IKK ) complex , which is composed of two kinases , IKK 1 and IKK 2 , and a regulatory subunit termed NF kappaB essential modulator ( NEMO ) . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
A complex rearrangement of the NEMO ( NF kappaB essential modulator ) gene accounts for 85 % of IP patients , and results in undetectable NEMO protein and absent NF kappaB activation . ^^^ Unravelling the molecular bases of other forms of EDA not associated with mutations in NEMO will possibly implicate other components of the NF kappaB signalling pathway . . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
BAFF induced NEMO independent processing of NF kappa B 2 in maturing B cells . ^^^ We show here that B cell activating factor ( BAFF ) activates this second pathway and that this requires the BAFF receptor ( BAFF R ) , the NF kappa B inducing kinase ( NIK ) and protein synthesis , but not NEMO . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Using jnk1 / 2 knockout ( jnk ( / ) ) and 1 kappa B kinase gamma / nemo ( / ) fibroblasts , we have determined the specific roles played by the JNK / AP 1 and NF kappa B / Rel pathways in this phenomenon . ^^^ On the other hand , lack of NF kappa B activity in nemo ( / ) fibroblasts did not affect the antagonistic effect of pro inflammatory cytokines against TGF beta . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Lymphotoxin beta receptor mediates NEMO independent NF kappaB activation . ^^^ Lymphotoxin beta receptor ( LTbetaR ) is a member of the tumor necrosis factor receptor ( TNFR ) superfamily that activates nuclear factor kappaB ( NF kappaB ) through the IkappaB kinase ( IKK ) complex , the core of which is comprised of IKK 1 , IKK 2 and NF kappaB essential modulator ( NEMO ) . ^^^ We demonstrate here that the LTbetaR signaling to NF kappaB activation does not necessarily require NEMO , which is essential for TNFR signaling . ^^^ In the absence of NEMO , the p 50 and RelB , but not RelA subunits of NF kappaB are found in the nuclear DNA binding complexes induced by the LTbetaR signaling . ^^^ Our results thus disclose NEMO independent NF kappaB activation by LTbetaR . . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Over 90 % of IP carrier females have a recurrent genomic deletion of exons 4 10 of the NEMO ( IKBKG IKKgamma ) gene , which encodes a regulatory component of the IkB kinase complex , required to activate the NF kB pathway . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Induction of the NF kappaB cascade by recruitment of the scaffold molecule NEMO to the T cell receptor . ^^^ Using ZAP 70 deficient T cells expressing a hybrid molecule between the SH 2 domain of ZAP 70 and NEMO / IKKgamma , we showed that targeting NEMO to the immunological synapse , and more specifically its 120 N terminal amino acids , was sufficient to selectively restore NF kappaB activation in response to TCR ligation . ^^^ Finally , we demonstrated that targeting of NEMO to the membrane of T cells was sufficient to induce constitutive NF kappaB activation . ^^^ This study shows that the localization of NEMO to the immunological synapse is important for TCR induced NF kappaB activation and offers a powerful system to dissect the NF kappaB cascade in T cells . . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
NF kappaB essential modulator ( NEMO ) is a scaffolding component of the IkappaB kinase complex required for NF kappaB activation in vitro . ^^^ Because NF kappaB activation is involved in B cell development and function , we set out to determine whether NEMO is required for these processes . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Here we show that LMP 1 activates NF kappaB in different NF kappaB essential modulator ( NEMO ) defective cell lines , but not in cells lacking both IkappaB kinase 1 ( IKK 1 ) and 2 ( IKK 2 ) . ^^^ Mutational studies reveal that CTAR 1 , but not CTAR 2 , mediates NEMO independent NF kappaB activation and that this process largely depends on IKK 1 . ^^^ Retroviral expression of LMP 1 mutants in cells lacking either functional NF kappaB inducing kinase ( NIK ) , NEMO , IKK 1 , or IKK 2 further illustrates distinct signals from the two activation regions of LMP 1 for persistent NF kappaB activation . ^^^ One originates in CTAR 2 , operates through the canonical NEMO dependent pathway , and induces NFKB 2 p100 production ; the second signal originates in CTAR 1 , utilizes NIK and IKK 1 , and induces the processing of p 100 . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
The IkappaB kinase ( IKK ) complex , consisting of two kinases , IKK1 / alpha and IKK2 / beta , and the NEMO / IKKgamma regulatory subunit , mediates NF kappaB activation by most known stimuli . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Previous studies have demonstrated that HHV 8 vFLIP K 13 interacts with several cellular signaling proteins involved in NF kappaB activation , such as receptor interacting protein , NF kappaB inducing kinase , IkappaB kinase ( IKK ) 1 , IKK 2 , and NF kappaB essential modulator ( NEMO ) . ^^^ On the other hand , vFLIP K 13 induced NF kappaB DNA binding activity is significantly reduced , although not absent , in cells deficient in IKK 1 , IKK 2 , and NEMO . ^^^ Furthermore , vFLIP K 13 induced NF kappaB transcriptional activity is only weakly present in IKK 1 deficient cells and almost completely absent in those deficient in IKK 2 and NEMO . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Nuclear role of 1 kappa B Kinase gamma / NF kappa B essential modulator ( IKK gamma / NEMO ) in NF kappa B dependent gene expression . ^^^ The 1 kappa B kinase ( IKK ) complex , which is composed of the two kinases IKK alpha and IKK beta and the regulatory subunit IKK gamma / nuclear factor kappa B ( NF kappa B ) essential modulator ( NEMO ) , is important in the cytokine induced activation of the NF kappa B pathway . ^^^ These results indicate that , in addition to the key role of IKK gamma / NEMO in regulating cytokine induced IKK activity , its ability to shuttle between the cytoplasm and the nucleus and to bind to CBP can lead to transcriptional repression of the NF kappa B pathway . . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Sequential modification of NEMO / IKKgamma by SUMO 1 and ubiquitin mediates NF kappaB activation by genotoxic stress . ^^^ Central to NF kappaB signaling pathways is NEMO / IKKgamma , the regulatory subunit of the cytoplasmic IkappaB kinase ( IKK ) complex . ^^^ While NF kappaB activation by genotoxic stress provides an attractive paradigm for nuclear to cytoplasmic signaling pathways , the mechanism by which nuclear DNA damage modulates NEMO to activate cytoplasmic IKK remains unknown . ^^^ Thus , genotoxic stress induces two independent signaling pathways , SUMO 1 modification and ATM activation , which work in concert to sequentially cause nuclear targeting and ubiquitylation of free NEMO to permit the NF kappaB survival pathway . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Mice treated intranasally with interleukin 10 or with a specific cell permeable peptide that blocks the association of the catalytic subunit IKKbeta with the regulatory protein NEMO showed a striking reduction of lung NF kappaB DNA binding activity , chemokine gene expression , and airway inflammation in response to RSV infection . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
In this regard , a cell permeable NBD peptide has been shown to block association of NEMO with the IKK complex and inhibit activation of NF kappaB . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Mutations in the NF kappaB essential modulator ( NEMO ) that lead to an inability to activate the NF kappaB pathway produce IP . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Recent studies implicate NOD 2 induced ubiquitination of the NF kappa B regulator NEMO as a potential means of manipulating the NF kappa B signal . . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Hypomorphic human mutations affecting one 1 kappa B kinase component , the NF kappa B essential modulator ( NEMO ) , result in impaired signaling from receptors required for ectodermal development and immune function . ^^^ The lack of any ectodermal phenotype , however , suggested a separation in the hematopoetic and ectodermal function of NEMO that leads to NF kappa B activation . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
The IKK complex is constituted of at least three subunits : two kinases , IKKalpha and IKKbeta , and one regulatory subunit ( NEMO / IKKgamma ) , and it constitutes an integrator of most if not all signals which activate NF kappaB . ^^^ This gene encodes a protein which interacts with NEMO and exhibits deubiquitinase activity , therefore strengthening the recent hypothesis of the role of non degradation linked ubiquitination in NF kappaB activation . . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
We studied patients with a variety of specific inherited immunodeficiencies resulting in a lack of leukocytes , or T , B , and / or NK lymphocytes , or polymorphonuclear cells , or a lack of expression of key molecules such as HLA class 2 , CD40L , NF kappaB essential modulator ( NEMO ) , and IL 1 receptor associated kinase 4 ( IRAK 4 ) . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Inhibition of NF kappa B activation by peptides targeting NF kappa B essential modulator ( nemo ) oligomerization . ^^^ NF kappa B essential modulator / IKK gamma ( NEMO / IKK gamma ) plays a key role in the activation of the NF kappa B pathway in response to proinflammatory stimuli . ^^^ To search for drugs inhibiting NF kappa B activation , we have rationally designed cell permeable peptides corresponding to the CC 2 and LZ subdomains that mimic the contact areas between NEMO subunits . ^^^ Our results provide the `` proof of concept ' ' for a new and promising strategy for the inhibition of NF kappa B pathway activation through targeting the oligomerization state of the NEMO protein . . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
In contrast , expression of a fusion protein composed of NEMO , a component of the IkappaB kinase complex , and the death domain of RIP ( NEMO DD ) can not restore TNF alpha induced NF kappaB activation in RIP deficient cells . ^^^ These results indicate that the role of RIP is to specifically recruit MEKK 3 to the TNF alpha receptor complex , whereas the forced recruitment of NEMO to the TNF alpha receptor complex is insufficient for TNF alpha induced NF kappaB activation . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Hypomorphic mutations in the zinc finger domain of NF kappaB essential modulator ( NEMO ) cause 10 linked hyper IgM syndrome with ectodermal dysplasia ( XHM ED ) . ^^^ This suggests that these NF kappaB components have different activation requirements and that IL 4 can augment some but not all NEMO dependent NF kappaB signaling . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
RESULTS : We demonstrate that NOD 2 activation leads to ubiquitinylation of NEMO , a key component of the NF kB signaling complex . ^^^ Lastly , we show functionally that RIP 2 induced ubiquitinylation of NEMO is at least in part responsible for RIP 2 mediated NF kB activation . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Here we report on the novel and specific interaction of HIF 2alpha , but not HIF 1alpha , with the NF kappaB essential modulator ( NEMO ) using immunoprecipitation , mammalian two hybrid , and in vitro protein interaction assays . ^^^ In contrast , HIF 2alpha overexpression does not alter NF kappaB signaling , suggesting that the functional consequence of the HIF 2alpha / NEMO interaction is limited to the HIF pathway . ^^^ The specificity of NEMO for HIF 2alpha represents one of the few known differential protein protein interactions between the HIF alpha proteins , which has important implications for the activity of HIF 2alpha and is also the first postulated NF kappaB independent role for NEMO . . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
The inhibitor of NF kappaB ( 1 kappaB ) kinase ( IKK ) complex consists of 3 subunits , IKK 1 , IKK 2 , and NF kappaB essential modulator ( NEMO ) , and is involved in the activation of NF kappaB by various stimuli . ^^^ Hepatocyte specific ablation of IKK 2 did not lead to impaired activation of NF kappaB or increased apoptosis after TNF alpha stimulation whereas conditional NEMO knockout resulted in complete block of NF kappaB activation and massive hepatocyte apoptosis . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
In contrast , NEMO binding domain ( NBD ) peptide , a specific inhibitor of NF kappaB signaling , did not affect COX 2 , RANKL , or OPG mRNA expression induced by IL 1alpha . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
The chimeric protein targets NEMO for polyubiquitination and thereby activates NF kappaB . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
The inhibitor of NF kappaB ( 1 kappaB ) kinase ( IKK ) complex consists of 3 subunits , IKK 1 , IKK 2 , and NF kappaB essential modulator ( NEMO ) , and is involved in the activation of NF kappaB by various stimuli . ^^^ Hepatocyte specific ablation of IKK 2 did not lead to impaired activation of NF kappaB or increased apoptosis after TNF alpha stimulation whereas conditional NEMO knockout resulted in complete block of NF kappaB activation and massive hepatocyte apoptosis . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
It is possible that the inheritance was autosomic dominant or it is a different mutation of NEMO ( NF kappa B essential modulator ) gene to a classical one , which was found in some affected men . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Zebrafish Ikk 1 forms complexes with NEMO that represses NF kappaB in vertebrate cells . ^^^ Indeed , truncation of its NEMO binding domain ( NBD ) restores NF kappaB dependent transcriptional activity and , consequently , the ikk 1 overexpressing phenotype . ^^^ Here , we report that Ikk 1 negatively regulates NF kappaB by sequestering NEMO from active IKK complexes , indicating that IKK 1 can function as a repressor of NF kappaB . . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Mutations in the NF kappaB essential modulator ( NEMO ) gene have recently been shown to be the cause of a group of ectodermal dysplasia and immunodeficiency disorders ( EDA ID ) . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
TNFalpha and IKKbeta mediated TANK / I TRAF phosphorylation : implications for interaction with NEMO / IKKgamma and NF kappaB activation . ^^^ Moreover , we show that TANK is phosphorylated by IKKbeta upon TNFalpha stimulation and that this modification negatively regulates TANK binding to NEMO ( NF kappaB essential modulator ) . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Upon genotoxic stress , a complex between PIDD , the kinase RIP 1 , and a component of the NF kappaB activating kinase complex , NEMO , is formed . ^^^ PIDD expression enhances genotoxic stress induced NF kappaB activation through augmented sumoylation and ubiquitination of NEMO . ^^^ Depletion of PIDD and RIP 1 , but not caspase 2 , abrogates DNA damage induced NEMO modification and NF kappaB activation . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Significant advances included the clinical prognosis in common variable immunodeficiency for patients presenting with lung pathology , the safety of live vaccines in partial DiGeorge syndrome , the report of patients with complete DiGeorge syndrome with the presence of peripheral blood T cells , the clinical spectrum of patients with NF kappaB essential modifier ( NEMO ) gene deficiency , the publication of a consensus algorithm for the management of hereditary angioedema , and the report of immune restoration syndrome in pediatric HIV infection . . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Incontinentia pigmenti ( IP ) is a rare neurocutaneous disorder caused by mutations in the NEMO ( NF kappaB essential modulator ) gene . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Some human XHED patients also have concurrent immunodeficiency , due to mutations in the NF kappaB essential modulator protein ( IKBKG ; formerly NEMO ) , which is also encoded on the 10 chromosome . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Anhidrotic ectodermal dysplasia with immunodeficiency ( EDA ID ) , either 10 linked recessive or autosomal dominant , is caused by hypomorphic mutations in NEMO or hypermorphic mutation in IKBA , respectively , both involved in nuclear factor kappaB ( NF kappaB ) activation . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Mutations of NEMO which do not abolish NF kappaB activity totally permit male survival , causing an allelic variant of IP called hypohidrotic ectodermal dysplasia and immunodeficiency ( HED ID ) . ^^^ The low T cell proliferation and CD40L expression corroborate the important role of NEMO / NF kappaB pathway in T cell homeostasis . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
A point mutation in NEMO associated with anhidrotic ectodermal dysplasia with immunodeficiency pathology results in destabilization of the oligomer and reduces lipopolysaccharide and tumor necrosis factor mediated NF kappa B activation . ^^^ The NEMO ( NF kappaB essential modulator ) protein plays a crucial role in the canonical NF kappaB pathway as the regulatory component of the IKK ( IkappaB kinase ) complex . ^^^ In addition , functional complementation assays using NEMO deficient pre B and T lymphocytes showed that the pathogenic mutation reduced TNF alpha and LPS induced NF kappaB activation by altering the assembly of the IKK complex . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
NF kappaB essential modulator ( NEMO ) , the regulatory subunit of the IkappaB kinase , is essential for NF kappaB activation . ^^^ NEMO deletion completely inhibited NF kappaB activation and sensitized keratinocytes to tumor necrosis factor ( TNF ) induced death but did not affect epidermal development . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Finally , three patients with a mutation in the IKBKG gene , encoding the NF kappaB essential modulator ( NEMO ) protein , were evaluated as disease controls and were almost uniformly below the standard deviation of healthy donors for all ligands tested . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
We show that NF kappaB essential modulator ( NEMO ) , the regulatory subunit of IkappaB kinase ( IKK ) ( which phosphorylates the NF kappaB inhibitor IkappaB ) , associates with activated ataxia telangiectasia mutated ( ATM ) after the induction of DNA double strand breaks . ^^^ Thus , regulated nuclear shuttling of NEMO links two signaling kinases , ATM and IKK , to activate NF kappaB by genotoxic signals . . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Sensing of Lys 63 linked polyubiquitination by NEMO is a key event in NF kappaB activation [ corrected ] . ^^^ NEMO is essential for NF kappaB activation , and NEMO dysfunction in humans is the cause of incontinentia pigmenti and hypohidrotic ectodermal dysplasia and immunodeficiency ( HED ID ) . ^^^ Here , we show that NEMO binds to Lys 63 but not Lys 48 linked polyubiquitin , and that single point mutations in NEMO that prevent binding to Lys 63 linked polyubiquitin also abrogates the binding of NEMO to RIP in tumour necrosis factor ( TNF ) alpha stimulated cells , the recruitment of IKK to TNF receptor ( TNF R ) 1 , and the activation of IKK and NF kappaB . ^^^ These results provide a mechanism for NEMO ' s critical role in IKK activation , and a key to understanding the link between cytokine receptor proximal signalling and IKK and NF kappaB activation . . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
The TFG protein , involved in oncogenic rearrangements , interacts with TANK and NEMO , two proteins involved in the NF kappaB pathway . ^^^ In this study by yeast two hybrid screening we identified NEMO and TANK , two proteins modulating the NF kappaB pathway , as novel TFG interacting proteins . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
In contrast , EDI DCs stimulated with the TLR 4 ligand lipopolysaccharide ( LPS ) showed normal downstream NF kappaB activity , DC maturation , and NEMO ubiquitination . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Moreover , NF kappaB activation was not increased in this case as shown by the levels of IkappaBalpha phosphorylation and NEMO ubiquitination . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
We report here mutations in the leucine zipper ( LZ ) domain of the NF kappaB essential modulator ( NEMO ) gene in three unrelated kindreds with XR MSMD . ^^^ IL 12 production was also impaired as the result of a specific defect in NEMO and NF kappaB / c Rel mediated CD 40 signaling after the stimulation of monocytes and dendritic cells by CD40L expressing T cells and fibroblasts , respectively . ^^^ They also demonstrate the importance of the T cell and CD40L triggered , CD 40 , and NEMO / NF kappaB / c Rel mediated induction of IL 12 by monocyte derived cells for protective immunity to mycobacteria in humans . . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
The gene that is mutated in patients with IP has been mapped to Xq 28 and encodes the NF kappaB essential modulator , NEMO . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
PIASy mediates NEMO sumoylation and NF kappaB activation in response to genotoxic stress . ^^^ SUMO 1 modification of NEMO ( NF kappaB essential modulator ) , the IkappaB kinase ( IKK ) regulatory subunit , is critical for activation of NF kappaB by genotoxic agents . ^^^ Here , we demonstrate that although small interfering RNAs ( siRNAs ) against PIASy ( protein inhibitor of activated STATy ) inhibit NEMO sumoylation and NF kappaB activation in response to genotoxic agents , overexpression of PIASy enhances these events . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Inhibition of canonical NF kappaB transcription factor activity through ablation of the essential scaffold protein NEMO arrests B cell development at the same stage as BAFF R deficiency . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
This IKK complex includes a catalytic heterodimer composed of IkappaB kinase 1 ( IKK 1 ) and IkappaB kinase 2 ( IKK 2 ) as well as a regulatory adaptor subunit , NF kappaB essential modulator . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
PDK 1 associated PKC recruits the IKK complex , whereas PDK 1 associated CARD 11 recruits the Bcl 10 MALT1 complex , thereby allowing activation of the IKK complex through Bcl 10 MALT1 dependent ubiquitination of the IKK complex subunit known as NEMO ( NF kappaB essential modifier ) . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Our recent findings show that attenuating IKK complex assembly , by using a short peptide termed NEMO binding domain ( NBD ) peptide , that blocks binding of IKK 2 and IKK 1 to IKKgamma / NEMO , inhibits NF kappaB activation , and arrests RANKL induced osteoclastogenesis . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Recruitment of the NF kappaB activating IKK signaling complex to the TNF receptor is shown to be driven by induced binding of NEMO , a regulatory component of this complex , to K 63 linked polyubiquitin chains attached to RIP 1 , a receptor associated adaptor protein ( Ea et al . , 2006 [ in a recent issue of Molecular Cell ] ; Li et al . , 2006 ; Wu et al . , 2006a ) . . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
This interaction apparently does not require the integrity of the IKK complex , as it was found to occur with extracts from cells deficient in the NF kappaB essential modulator , one of the components of the IKK complex . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
The phosphorylation of IkappaBalpha on Ser ( 32 ) and Ser ( 36 ) is initiated by an IkappaB kinase ( IKK ) complex that includes a catalytic heterodimer composed of IkappaB kinase 1 ( IKK 1 ) and IkappaB kinase 2 ( IKK 2 ) as well as a regulatory adaptor subunit , NF kappaB essential modulator . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
In this patient with OL EDA ID , we detected the same NF kappaB essential modulator stop codon hypomorphic mutation identified in the previous patient . ^^^ Both syndromes are allelic and are associated with mutations in NF kappaB essential modulator , with a genotype phenotype correlation in hemizygous males . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Conversely , in NF kappaB essential modulator / ( NEMO / ) fibroblasts , lack of NF kappaB activation did not influence the antagonism exerted by TNF alpha against TGF beta but prevented repression of basal COL1A2 gene expression . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
Geldanamycin pretreatment led to a proteasome dependent decrease in the levels of several TNFR 1 interacting proteins including the kinases receptor interacting protein , inhibitor of kappa B kinase alpha , inhibitor of kappa B kinase beta , and to a lesser extent the adaptors NF kappaB essential modulator and tumor necrosis factor receptor associated factor 2 . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
We have identified TWEAK as an inducer of constitutive NF kappaB activation by expression cloning , and we report here sequential regulation by TWEAK of two separate signaling cascades for NF kappaB activation , the NF kappaB essential modulator dependent and independent signaling pathways . ^^^ This long lasting activation is accompanied by the proteasome mediated processing of NF kappaB2 / p100 , which does not depend on the NF kappaB essential modulator but requires IkappaB kinase 1 and functional NF kappaB inducing kinase activity . ^^^
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K9 and P19838 Pubmed SVM Score :0.0
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