| Interacting proteins: Q9Y297 and P25963 |
Pubmed |
SVM Score :0.53766528 |
| FWD 1 ( the mouse homolog of Drosophila Slimb and Xenopus betaTrCP , a member of the F box and WD 40 repeat containing family of proteins , and a component of the SCF ubiquitin ligase complex ) was recently shown to interact with IkappaBalpha and thereby to promote its ubiquitination and degradation . 0.53766528^^^ |
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| Interacting proteins: Q9Y297 and P25963 |
Pubmed |
SVM Score :0.62374623 |
| Here , we show that FWD 1 ( a mouse homologue of Slimb / betaTrCP ) , a member of the F box / WD40 repeat proteins , is associated specifically with IkappaBalpha only when IkappaBalpha is phosphorylated . 0.62374623^^^ |
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| Interacting proteins: Q9Y297 and P25963 |
Pubmed |
SVM Score :0.53302952 |
| The structural requirements for the interactions of FWD 1 with IkappaBalpha and with Skp 1 have now been investigated further . 0.53302952^^^ |
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| Interacting proteins: Q9Y297 and P25963 |
Pubmed |
SVM Score :0.0 |
| Signal induced ubiquitination of IkappaBalpha by the F box protein Slimb / beta TrCP . ^^^ We report here the identification of an IkappaB ubiquitin ( Ub ) ligase complex containing the F box / WD40 repeat protein , beta TrCP , a vertebrate homolog of Drosophila Slimb . beta TrCP binds to IkappaBalpha only when the latter is specifically phosphorylated by an IkappaB kinase complex . ^^^ Moreover , immunopurified beta TrCP ubiquitinates phosphorylated IkappaBalpha at specific lysines in the presence of Ub activating ( E 1 ) and conjugating ( Ubch 5 ) enzymes . ^^^ A beta TrCP mutant lacking the F box inhibits the signal induced degradation of IkappaBalpha and subsequent activation of NF kappaB dependent transcription . ^^^ These biochemical and genetic data strongly suggest that Slimb / beta TrCP is the specificity determinant for the signal induced ubiquitination of IkappaBalpha . . ^^^ |
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| Interacting proteins: Q9Y297 and P25963 |
Pubmed |
SVM Score :0.0 |
| Inducible degradation of IkappaBalpha by the proteasome requires interaction with the F box protein h betaTrCP . ^^^ We provide evidence that a human F box protein , h betaTrCP , a component of Skp 1 Cullin F box protein ( SCF ) complexes , a new class of E 3 ubiquitin ligases , is essential for inducible degradation of IkappaBalpha . betaTrCP associates with Ser 32 Ser36 phosphorylated , but not with unmodified IkappaBalpha or Ser 32 Ser36 phosphorylation deficient mutants . ^^^ Expression of a F box deleted betaTrCP inhibits IkappaBalpha degradation , promotes accumulation of phosphorylated Ser 32 Ser36 IkappaBalpha , and prevents NF kappaB dependent transcription . ^^^ Our findings indicate that betaTrCP is the adaptor protein required for IkappaBalpha recognition by the SCFbetaTrCP E 3 complex that ubiquitinates IkappaBalpha and makes it a substrate for the proteasome . . ^^^ |
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| Interacting proteins: Q9Y297 and P25963 |
Pubmed |
SVM Score :0.0 |
| A complex containing betaTrCP recruits Cdc 34 to catalyse ubiquitination of IkappaBalpha . ^^^ In the presence of ubiquitin activating enzyme and the protein complex containing betaTrCP , polyubiquitination of IkappaBalpha peptide was dependent on the presence of Cdc 34 , while Ubc 5 only stimulated mono and di ubiquitination . . ^^^ |
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| Interacting proteins: Q9Y297 and P25963 |
Pubmed |
SVM Score :0.0 |
| Therefore , these results indicate that beta TrCP plays a critical role in the activation of NF kappaB by assembling the ubiquitin ligase complex for both phosphorylated IkappaBalpha and IkappaBbeta . . ^^^ |
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| Interacting proteins: Q9Y297 and P25963 |
Pubmed |
SVM Score :0.0 |
| Homodimer of two F box proteins betaTrCP 1 or betaTrCP 2 binds to IkappaBalpha for signal dependent ubiquitination . ^^^ We found previously that overexpression of an F box protein betaTrCP 1 and the structurally related betaTrCP 2 augments ubiquitination of phosphorylated IkappaBalpha ( pIkappaBalpha ) induced by tumor necrosis factor alpha ( TNF alpha ) , but the relationship of the two homologous betaTrCP proteins remains unknown . ^^^ These results indicate that not only betaTrCP 1 but also betaTrCP 2 participates in the ubiquitination dependent destruction of IkappaBalpha by forming SCF ( betaTrCP 1 betaTrCP1 ) and SCF ( betaTrCP 2 betaTrCP2 ) ubiquitin ligase complexes . . ^^^ |
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| Interacting proteins: Q9Y297 and P25963 |
Pubmed |
SVM Score :0.0 |
| Beta catenin , IkappaBalpha , and HIV Vpu are recruited to the ubiquitin proteasome degradation pathway by betaTRCP , one of the components of the ubiquitin ligase complex . betaTRCP 2 , a related gene of betaTRCP , was cloned and characterized . ^^^ |
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| Interacting proteins: Q9Y297 and P25963 |
Pubmed |
SVM Score :0.0 |
| SCF ( beta TRCP ) and phosphorylation dependent ubiquitinationof 1 kappa B alpha catalyzed by Ubc 3 and Ubc 4 . ^^^ The SCF beta TRCP complex is the ubiquitin ligase responsible for mediating phosphorylation dependent ubiquitination of 1 kappa B alpha . ^^^ We demonstrate specific ubiquitination of 1 kappa B alpha by Ubc 3 and Ubc 4 in a phosphorylation and SCF beta TRCP dependent manner and that both are capable of associating with the SCF beta TRCP complex isolated from human cells . ^^^ Our results also suggest that ubiquitin is transferred directly from the Ubc to phospho 1 kappa B alpha in a SCF beta TRCP dependent reaction . ^^^ |
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| Interacting proteins: Q9Y297 and P25963 |
Pubmed |
SVM Score :0.0 |
| Shared pathways of IkappaB kinase induced SCF ( betaTrCP ) mediated ubiquitination and degradation for the NF kappaB precursor p 105 and IkappaBalpha . p 105 ( NFKB 1 ) acts in a dual way as a cytoplasmic IkappaB molecule and as the source of the NF kappaB p 50 subunit upon processing . p 105 can form various heterodimers with other NF kappaB subunits , including its own processing product , p 50 , and these complexes are signal responsive . ^^^ |
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| Interacting proteins: Q9Y297 and P25963 |
Pubmed |
SVM Score :0.0 |
| Here we show that the F box protein betaTrCP , the receptor component of the SCF E 3 ubiquitin ligase responsible for IkappaBalpha and beta catenin degradation , is colocalized in the nucleus with ATF 4 , a member of the ATF CREB bZIP family of transcription factors , and controls its stability . ^^^ |
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| Interacting proteins: Q9Y297 and P25963 |
Pubmed |
SVM Score :0.0 |
| One domain of Protac 1 contains the 1 kappa B alpha phosphopeptide that is recognized by the F box protein beta TRCP , whereas the other domain is composed of ovalicin . ^^^ |
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| Interacting proteins: Q9Y297 and P25963 |
Pubmed |
SVM Score :0.0 |
| Although the mechanisms that underlie processing of p 105 are largely obscure , it is clear that NEDDylation and the coordinated activity of SCF ( beta TrCP ) on both p 105 and IkappaBalpha serve as an important regulatory mechanism controlling NF kappaB activity . . ^^^ |
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| Interacting proteins: Q9Y297 and P25963 |
Pubmed |
SVM Score :0.0 |
| The phospho 1 kappa B alpha generated by UV is only detectable by expressing a Delta F box mutant of the ubiquitin ligase beta TrCP , which serves as a specific substrate trap for serine 32 and 36 phosphorylated 1 kappa B alpha . ^^^ |
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| Interacting proteins: Q9Y297 and P25963 |
Pubmed |
SVM Score :0.0 |
| Interestingly , however , betaTrCP affinity for the IKK phosphorylated sequence on p 105 is substantially lower than that on IkappaBalpha . ^^^ Thus , it appears that reduced p 105 recruitment of betaTrCP and subsequent ubiquitination may contribute to delayed p 105 proteolysis after TNF alpha stimulation relative to that for IkappaBalpha . . ^^^ |
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| Interacting proteins: Q9Y297 and P25963 |
Pubmed |
SVM Score :0.0 |
| TIP120A greatly reduced the ubiquitination of phosphorylated IkappaBalpha by SCF ( beta TrCP ) ubiquitin ligase . ^^^ |
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| Interacting proteins: Q9Y297 and P25963 |
Pubmed |
SVM Score :0.0 |
| This Protac consisted of an SCF ( beta TRCP ) binding phosphopeptide derived from IkappaBalpha linked to ovalicin , which covalently binds MetAP 2 . ^^^ |
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| Interacting proteins: Q9Y297 and P25963 |
Pubmed |
SVM Score :0.0 |
| We showed that the expression of a Vpu green fluorescent fusion protein prevented the proteosomal degradation of betaTrCP substrates such as beta catenin , IkappaBalpha , and ATF 4 , which are normally directly targeted to the proteasome for degradation . ^^^ |
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| Interacting proteins: Q9Y297 and P25963 |
Pubmed |
SVM Score :0.0 |
| We hypothesized that the E 3 ligase , beta transducin repeat containing protein 1 ( beta TrCP 1 ) , was a rate determining mediator that regulates the ubiquitin mediated degradation of IkappaBalpha ( in VSMC ) . ^^^ METHODS AND RESULTS : Upregulation of beta TrCP 1 accelerated the rate of IkappaBalpha degradation , leading to increased NF kappaB activity . ^^^ |
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| Interacting proteins: Q9Y297 and P25963 |
Pubmed |
SVM Score :0.0 |
| BACKGROUND : The ubiquitin proteasome pathway is important in regulating protein signaling pathways that are involved in tumorigenesis . beta transducin repeat containing proteins ( beta TrCP ) are components of the ubiquitin ligase complex targeting beta catenin and IkappaBalpha for proteasomal degradation and are thus a negative regulator of Wnt / beta catenin signaling and a positive regulator of NF kappaB signaling . ^^^ |
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| Interacting proteins: Q9Y297 and P25963 |
Pubmed |
SVM Score :0.0 |
| Here , we identified that a phosphorylated form of IkappaBalpha ( pIkappaBalpha ) , an inhibitor of NF kappaB , and SCF ( beta TrCP ) , the ubiquitin ligase of pIkappaBalpha , are components of LB in brains of PD patients . ^^^ |
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| Interacting proteins: Q9Y297 and P25963 |
Pubmed |
SVM Score :0.0 |
| Canonical inducible NF kappaB activation involves IkappaB kinase ( IKK ) dependent dual phosphorylation of Ser 32 and 36 of IkappaBalpha to cause its beta TrCP dependent ubiquitylation and proteasomal degradation . ^^^ We recently reported that constitutive NF kappaB ( p50 / c Rel ) activity in WEHI 231 B cells is maintained through proteasome inhibitor resistant ( PIR ) IkappaBalpha degradation in a manner that requires Ser 32 and 36 , without the requirement of a direct interaction with beta TrCP . ^^^ |
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| Interacting proteins: Q9Y297 and P25963 |
Pubmed |
SVM Score :0.0 |
| In addition , we identified a phosphorylated form of IkappaBalpha ( pIkappaBalpha ) , an inhibitor of the NF kappaB signaling pathway , and the components of the SCF ( beta TrCP ) , ubiquitin ligase of pIkappaBalpha , are novel protein components in LBs . ^^^ |
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| Interacting proteins: Q9Y297 and P25963 |
Pubmed |
SVM Score :0.0 |
| In contrast , stabilization of beta catenin and IkappaBalpha , two previously reported beta Trcp 1 substrates , does not occur in the absence of beta Trcp 1 and instead requires the additional silencing of beta Trcp 2 by siRNA . ^^^ |
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| Interacting proteins: Q9Y297 and P25963 |
Pubmed |
SVM Score :0.0 |
| We have now generated mice deficient in beta TrCP 1 and shown that the degradation of 1 kappa B alpha and 1 kappa B beta is reproducibly , but not completely , impaired in the cells of these animals . ^^^ |
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| Interacting proteins: Q9Y297 and P25963 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q9Y297 and P25963 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q9Y297 and P25963 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q9Y297 and P25963 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q9Y297 and P25963 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q9Y297 and P25963 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q9Y297 and P25963 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q9Y297 and P25963 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q9Y297 and P25963 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q9Y297 and P25963 |
Pubmed |
SVM Score :0.0 |
| NA |
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