| Interacting proteins: Q9Y297 and P35222 |
Pubmed |
SVM Score :0.61019189 |
| Consistent with recent reports indicating that Xenopus and Drosophila beta Trcp homologs act as negative regulators of the Wnt / beta catenin signaling pathway , we report here that human beta Trcp interacts with beta catenin in vivo . 0.61019189^^^ |
|
| Interacting proteins: Q9Y297 and P35222 |
Pubmed |
SVM Score :1.2459857 |
| The F box protein beta TrCP associates with phosphorylated beta catenin and regulates its activity in the cell . 1.2459857^^^ |
|
| Interacting proteins: Q9Y297 and P35222 |
Pubmed |
SVM Score :0.66985085 |
| Here we show that beta catenin stabilizes the mRNA encoding the F box protein betaTrCP 1 , and identify the RNA binding protein CRD BP ( coding region determinant binding protein ) as a previously unknown target of beta catenin / Tcf transcription factor . 0.66985085^^^ |
|
| Interacting proteins: Q9Y297 and P35222 |
Pubmed |
SVM Score :0.0 |
| We identified seven alterations : two in CTNNB 1 , three in APC , and two in hTRCP 1 ( also known as BTRC ) which controls the degradation of CTNNB 1 . ^^^ |
|
| Interacting proteins: Q9Y297 and P35222 |
Pubmed |
SVM Score :0.0 |
| We investigated 37 malignant melanomas ( 15 primary tumors and 22 metastases ) for alterations of 4 genes encoding members of this pathway , i . e . , CTNNB 1 ( beta catenin gene , 3p22 . 1 ) , APC ( adenomatous polyposis coli gene , 5q22 . 2 ) , BTRC ( beta transducin repeat containing protein gene , 10q24 . 3 ) and ICAT ( inhibitor of beta catenin and Tcf 4 , 1p36 . 2 ) . ^^^ Molecular genetic analysis of malignant melanomas for aberrations of the WNT signaling pathway genes CTNNB 1 , APC , ICAT and BTRC . ^^^ |
|
| Interacting proteins: Q9Y297 and P35222 |
Pubmed |
SVM Score :0.0 |
| Screening a maternal Xenopus expression library for activities that synergize with low levels of injected beta catenin , we have isolated a clone encoding the C terminal end of 10 beta TrCP 2 , a highly conserved protein belonging to the F box / WD40 family of ubiquitin ligase specificity factors . ^^^ |
|
| Interacting proteins: Q9Y297 and P35222 |
Pubmed |
SVM Score :0.0 |
| Here we show that phosphorylated beta catenin is specifically recognized by beta Trcp , an F box / WD40 repeat protein that also associates with Skp 1 , an essential component of the ubiquitination apparatus . beta catenin harboring mutations at the critical phosphoserine residues escapes recognition by beta Trcp , thus providing a molecular explanation for why these mutations cause beta catenin accumulation that leads to cancer . ^^^ Inhibition of endogenous beta Trcp function by a dominant negative mutant stabilizes beta catenin , activates Wnt / beta catenin signaling , and induces axis formation in Xenopus embryos . ^^^ Therefore , beta Trcp plays a central role in recruiting phosphorylated beta catenin for degradation and in dorsoventral patterning of the Xenopus embryo . . ^^^ |
|
| Interacting proteins: Q9Y297 and P35222 |
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 . ^^^ |
|
| Interacting proteins: Q9Y297 and P35222 |
Pubmed |
SVM Score :0.0 |
| Beta TrCP , an F box protein of the SCF E 3 ubiquitin ligase complex , was recently shown to play a role in the turnover of beta catenin . ^^^ We show here that a deletion mutant of beta TrCP , lacking the F box , can stabilize the endogenous beta catenin leading to its nuclear translocation and induction of beta catenin / LEF 1 directed transcription , without affecting the levels of plakoglobin . ^^^ However , when plakoglobin was overexpressed , it readily associated with beta TrCP , efficiently competed with beta catenin for binding to beta TrCP and became polyubiquitinated . ^^^ These results suggest that while both plakoglobin and beta catenin can comparably interact with beta TrCP and the ubiquitination system , the sequestration of plakoglobin by the membrane cytoskeleton system renders it inaccessible to the proteolytic machinery and stabilizes it . . ^^^ |
|
| Interacting proteins: Q9Y297 and P35222 |
Pubmed |
SVM Score :0.0 |
| Wnt / beta catenin signaling induces the expression and activity of betaTrCP ubiquitin ligase receptor . ^^^ Beta transducing repeat containing protein ( betaTrCP ) targets the ubiquitination and subsequent degradation of both beta catenin and IkappaB , thereby playing an important role in beta catenin / Tcf and NF kappaB dependent signaling . ^^^ Here evidence is presented that beta catenin / Tcf signaling elevates the expression of betaTrCP mRNA and protein in a Tcf dependent manner , which does not require betaTrCP transcription . ^^^ Induction of betaTrCP expression by the beta catenin / Tcf pathway results in an accelerated degradation of the wild type beta catenin , suggesting that the negative feedback loop regulation may control the beta catenin / Tcf pathway . ^^^ This signaling also upregulated NF kappaB transactivation without affecting the activity of IkappaB kinase , thereby establishing that the maintenance of the betaTrCP level is important for coordination between beta catenin / Tcf and NF kappaB signaling . . ^^^ |
|
| Interacting proteins: Q9Y297 and P35222 |
Pubmed |
SVM Score :0.0 |
| BetaTrCP and HOS are closely related F box proteins , which play key roles in ubiquitination and degradation of beta catenin and IkappaB through associating with those phosphorylated substrates and recruiting SCF E 3 ubiquitin ligase . ^^^ Here we report that activation of Wnt / beta catenin signal transduction pathway elevates betaTrCP levels but inhibits expression of HOS in 293T cells . ^^^ In the NIH3T3 cells , which express HOS , but not betaTrCP , Wnt / beta catenin signaling leads to inhibition of HOS promoter activity and NF kappaB driven transcription as well as to stabilization of beta catenin . ^^^ |
|
| Interacting proteins: Q9Y297 and P35222 |
Pubmed |
SVM Score :0.0 |
| CK 2 dependent phosphorylation of the E 2 ubiquitin conjugating enzyme UBC3B induces its interaction with beta TrCP and enhances beta catenin degradation . ^^^ |
|
| Interacting proteins: Q9Y297 and P35222 |
Pubmed |
SVM Score :0.0 |
| Serine 33 and 37 of beta catenin are GSK 3 phosphorylation sites that serve as recognition sites for the beta TRCP ubiquitin ligase complex , which ultimately triggers beta catenin degradation . ^^^ In spite of the fact that CKI epsilon was found as a positive regulator of the Wnt pathway , mutational analysis suggests that mutation of Ser 45 regulates beta catenin stability by inhibiting the ability of GSK 3 to phosphorylate Ser 33 and 37 , thereby disrupting the interaction between beta catenin , beta TRCP and Axin . 1 propose that phosphorylation of Ser 45 by CKI epsilon plays an important role in regulating beta catenin stability . . ^^^ |
|
| Interacting proteins: Q9Y297 and P35222 |
Pubmed |
SVM Score :0.0 |
| By engineering a chimeric protein with the beta catenin binding domain of E cadherin fused to betaTrCP ubiquitin protein ligase , the stable beta catenin mutant was recruited to the cellular SCF ( Skp 1 , Cullin 1 , and F box containing substrate receptor ) ubiquitination machinery for ubiquitination and degradation . ^^^ Remarkably , conditional expression of betaTrCP E cadherin under the control of a tetracycline repressive promoter in DLD 1 cells selectively knocked down the cytosolic , but not membrane associated subpopulation of beta catenin . ^^^ |
|
| Interacting proteins: Q9Y297 and P35222 |
Pubmed |
SVM Score :0.0 |
| HIV 1 Vpu sequesters beta transducin repeat containing protein ( betaTrCP ) in the cytoplasm and provokes the accumulation of beta catenin and other SCFbetaTrCP substrates . ^^^ 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 . ^^^ |
|
| Interacting proteins: Q9Y297 and P35222 |
Pubmed |
SVM Score :0.0 |
| Upregulation of Wnt 1 resulted in beta catenin mediated activation of Tcf 4 , leading to increased beta TrCP 1 expression and NF kappaB activity . ^^^ Furthermore , VSMCs harboring a Tcf 4 mutant lacking a beta catenin binding domain exhibited a significant reduction in beta TrCP 1 expression along with abolishment of NF kappaB activity . ^^^ |
|
| Interacting proteins: Q9Y297 and P35222 |
Pubmed |
SVM Score :0.0 |
| Degradation of phosphorylated beta catenin is initiated by interaction through the WD 40 repeat of a F box protein beta TrCP , a component of SCF ubiquitin ligase complex . ^^^ In the search for efficient treatment and prevention of malignancies associated with increased levels of cytoplasmic beta catenin , we created chimeric F box fusion proteins by replacing the WD 40 repeat of beta TrCP with the beta catenin binding domains of Tcf 4 and E cadherin . ^^^ |
|
| Interacting proteins: Q9Y297 and P35222 |
Pubmed |
SVM Score :0.0 |
| In several tumour types , TCF / beta catenin activation is caused by mutations in either adenomatous polyposis coli ( APC ) , beta catenin exon 3 , AXIN 1 , AXIN 2 or beta transducin repeat containing protein ( beta TrCP ) . ^^^ |
|
| Interacting proteins: Q9Y297 and P35222 |
Pubmed |
SVM Score :0.0 |
| Associations among beta TrCP , an E 3 ubiquitin ligase receptor , beta catenin , and NF kappaB in colorectal cancer . ^^^ 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 . ^^^ We analyzed expression of beta TrCP in colorectal cancers and its association with types of beta catenin subcellular localization , an indirect measure of activation . ^^^ Increased beta TrCP 1 levels were statistically significantly associated with beta catenin activation ( P = . 023 ) and decreased apoptosis ( P = . 035 ) . beta TrCP accumulated in the nuclei of tumor cells that contained increased levels of beta TrCP 1 mRNA and the active form of NF kappaB . ^^^ CONCLUSION : In colorectal cancer , increased expression of beta TrCP 1 is associated with activation of both beta catenin and NF kappaB , suggesting that the integration of these signaling pathways by increased beta TrCP expression may contribute to an inhibition of apoptosis and tumor metastasis . . ^^^ |
|
| Interacting proteins: Q9Y297 and P35222 |
Pubmed |
SVM Score :0.0 |
| STD and TRNOESY NMR studies on the conformation of the oncogenic protein beta catenin containing the phosphorylated motif DpSGXXpS bound to the beta TrCP protein . beta TrCP is the F box protein component of an Skp1 / Cul1 / F box ( SCF ) type ubiquitin ligase complex . ^^^ Biochemical studies have suggested that beta TrCP targets the oncogenic protein beta catenin for ubiquitination and followed by proteasome degradation . ^^^ To further elucidate the basis of this interaction , a complex between a 32 residue peptide from beta catenin containing the phosphorylated motif DpSGXXpS ( P beta Cat 17 48 ) and beta TrCP was studied using Saturation Transfer Difference ( STD ) Nuclear Magnetic Resonance ( NMR ) experiments . ^^^ These findings are in keeping with a recently published 10 ray structure of a shorter beta catenin fragment with the beta TrCP 1 Skp1 complex and with the earlier findings from mutagenesis and activity assays . ^^^ |
|
| Interacting proteins: Q9Y297 and P35222 |
Pubmed |
SVM Score :0.0 |
| We analyzed 23 hepatoblastoma biopsies for which matching liver tissue was available , 6 hepatoblastoma cell lines , and 3 human fetal liver samples . beta TRCP and NKD 1 were highly expressed in all hepatoblastoma samples , independent of the beta catenin mutational status , in comparison with their nontumorous counterparts . beta TRCP mRNA overexpression was associated with accumulation of intracytoplasmic and nuclear beta TrCP protein . ^^^ |
|
| Interacting proteins: Q9Y297 and P35222 |
Pubmed |
SVM Score :0.0 |
| Considered with evidence that the distinct Cullin 1 based SCF ( beta TrCP ) complex regulates beta catenin stability , our data on the stability of Dishevelled demonstrates that two distinct ubiquitin ligase complexes regulate the Wnt beta catenin pathway . . ^^^ |
|
| Interacting proteins: Q9Y297 and P35222 |
Pubmed |
SVM Score :0.0 |
| It is established that Ser 45 phosphorylation by casein kinase 1 ( CKI ) initiates phosphorylation at Thr 41 , Ser 37 , and Ser 33 by glycogen synthase kinase 3 ( GSK 3 ) and that phosphorylated Ser 37 and Ser 33 are recognized by the F box protein beta TrCP , a component of a ubiquitin ligase complex that mediates beta catenin degradation . ^^^ |
|
| Interacting proteins: Q9Y297 and P35222 |
Pubmed |
SVM Score :0.0 |
| Phosphorylation of beta Catenin at sites Ser 33 and Ser 37 on the DSGXXS motif is required for the interaction of beta Catenin with the ubiquitin ligase SCF ( beta TrCP ) . beta TrCP is involved in the ubiquitination and proteasome targeting of the oncogenic protein beta Catenin , the accumulation of which has been implicated in various human cancers . ^^^ These findings are in excellent agreement with a recently published NMR structure required for the interaction of beta Catenin with the SCF ( beta TrCP ) protein . . ^^^ |
|
| Interacting proteins: Q9Y297 and P35222 |
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 . ^^^ |
|
| Interacting proteins: Q9Y297 and P35222 |
Pubmed |
SVM Score :0.0 |
| Structure of a beta TrCP 1 Skp1 beta catenin complex : destruction motif binding and lysine specificity of the SCF ( beta TrCP 1 ) ubiquitin ligase . ^^^ The F box protein beta TrCP 1 recognizes the doubly phosphorylated DpSGphiXpS destruction motif , present in beta catenin and IkappaB , and directs the SCF ( beta TrCP 1 ) to ubiquitinate these proteins at specific lysines . ^^^ The 3 . 0 A structure of a beta TrCP 1 Skp1 beta catenin complex reveals the basis of substrate recognition by the beta TrCP 1 WD40 domain . ^^^ |
|
| Interacting proteins: Q9Y297 and P35222 |
Pubmed |
SVM Score :0.0 |
| Impaired degradation of inhibitory subunit of NF kappa B ( 1 kappa B ) and beta catenin as a result of targeted disruption of the beta TrCP 1 gene . beta TrCP 1 ( also known as Fbw1a or FWD 1 ) is the F box protein component of an Skp1 / Cul1 / F box ( SCF ) type ubiquitin ligase complex . ^^^ Although biochemical studies have suggested that beta TrCP 1 targets inhibitory subunit of NF kappa B ( 1 kappa B ) proteins and beta catenin for ubiquitylation , the physiological role of beta TrCP 1 in mammals has remained unclear . ^^^ The subcellular localization of beta catenin was altered markedly in beta TrCP 1 / cells . ^^^ These results suggest that beta TrCP 1 contributes to , but is not absolutely required for , the degradation of 1 kappa B and beta catenin and the consequent regulation of the NF kappa B and Wnt signaling pathways , respectively . ^^^ |
|
| Interacting proteins: Q9Y297 and P35222 |
Pubmed |
SVM Score :0.0 |
| All these mutations result in the synthesis of unphosphorylated beta catenin that escapes recognition by the beta transducin repeat protein ( beta TrCP 1 ) , the receptor of an ubiquitin . ^^^ These results show that the overexpression of Delta F beta TrCP 1 or beta TrCP 1 in vivo induce tumors through beta catenin activation . . ^^^ |
|
| Interacting proteins: Q9Y297 and P35222 |
Pubmed |
SVM Score :0.0 |
| An F box protein , FWD 1 , mediates ubiquitin dependent proteolysis of beta catenin . beta catenin plays an essential role in the Wingless / Wnt signaling cascade and is a component of the cadherin cell adhesion complex . ^^^ Here we show that FWD 1 ( the mouse homologue of Slimb / betaTrCP ) , an F box / WD40 repeat protein , specifically formed a multi molecular complex with beta catenin , Axin , GSK 3beta and APC . ^^^ Mutations at the signal induced phosphorylation site of beta catenin inhibited its association with FWD 1 . ^^^ FWD 1 facilitated ubiquitination and promoted degradation of beta catenin , resulting in reduced cytoplasmic beta catenin levels . ^^^ In contrast , a dominant negative mutant form of FWD 1 inhibited the ubiquitination process and stabilized beta catenin . ^^^ |
|
| Interacting proteins: Q9Y297 and P35222 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q9Y297 and P35222 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q9Y297 and P35222 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q9Y297 and P35222 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q9Y297 and P35222 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q9Y297 and P35222 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q9Y297 and P35222 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q9Y297 and P35222 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q9Y297 and P35222 |
Pubmed |
SVM Score :0.0 |
| NA |
|