| Interacting proteins: Q9Y297 and Q13485 |
Pubmed |
SVM Score :0.0 |
| SCF ( beta TrCP 1 ) controls Smad 4 protein stability in pancreatic cancer cells . ^^^ Here we report that SCF ( beta TrCP 1 ) , a ubiquitin ( E 3 ) ligase , is a critical determinant for Smad 4 protein degradation in pancreatic cancer cells . ^^^ We found that F box protein beta TrCP 1 in this E 3 ligase interacted with Smad 4 and that SCF ( beta TrCP 1 ) inhibited TGF beta biological activity in pancreatic cancer cells by decreasing Smad 4 stability . ^^^ By analyzing pancreatic tumor derived Smad 4 mutants , we found that most point mutated Smad 4 proteins , except those within or very close to a mutation cluster region , exhibited higher interaction affinity with beta TrCP 1 and significantly elevated protein ubiquitination by SCF ( beta TrCP 1 ) . ^^^ Furthermore , AsPC 1 and Caco 2 , two cancer cell lines harboring Smad 4 point mutations , exhibited rapid Smad 4 protein degradation due to the effect of SCF ( beta TrCP 1 ) . ^^^ |
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| Interacting proteins: Q9Y297 and Q13485 |
Pubmed |
SVM Score :0.0 |
| Importantly , we found that beta transducin repeat containing protein 1 ( beta TrCP 1 ) , an F box protein in the ubiquitin E 3 ligase Skp 1 Cullin F box protein ( SCF ) complex , directly interacts with and acts as a critical determinant for degradation of both mutated SMAD 4 proteins . ^^^ In addition , small interference RNA ( siRNA ) triggered endogenous beta TrCP 1 suppression increased the protein expression level of both overexpressed SMAD 4 mutants and endogenous mutated SMAD 4 protein in acute myelogenous leukemia cells . ^^^ These data suggest that mutated SMAD 4 proteins undergo rapid degradation in acute myelogenous leukemia cells via SCF ( beta TrCP 1 ) E 3 ligase mediated protein ubiquitination ( or ubiquitylation ) and subsequent proteasomal degradation . . ^^^ |
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