IndraLab

Statements

COPS5 inhibits SMAD7. 7 / 7
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"The Smad7 transcriptional regulation is mediated by the Ski protein, which inhibits the Smad7 promoter, and the posttransductional regulation is mediated through the effects of Smurf and Jab1 proteins, which promote Smad7 degradation [XREF_BIBR, XREF_BIBR]."
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"As expected, silencing of both CUL4B and Jab1 decreased Jab1 immunofluorescence signals and increased Smad7 signals to levels almost equal to those observed in control RNAi treated cells."
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"For example, TIEG and Foxp3 enhance TGF-beta signaling through the repression of Smad7 gene expression, AMSH and AMSH2 interact with inhibitory Smads and suppress their effects, and Jab1 and CSN5 induce Smad7 degradation."
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"However, Jab1 was also shown to interact with and induce the degradation of Smad7, resulting in increased TGF-beta signaling [XREF_BIBR]."
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"Jab1, as a component of Smurf 1/2 E3 ligases, promotes Smad7 degradation [34], serving to negatively regulate BMP signaling by interfering with the phosphorylation of R-Smads [42,43]."
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"Together, these data establish Jab1 as an ubiquitination target for the CUL4B ubiquitin ligase complex.In addition to its role in deneddylation [32,33], Jab1 and CSN5 has been shown to bind to Smad7, [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Moreover, Jab1/CSN5 can induce the degradation of two important downstream molecules, Smad4 and Smad7, and affect transforming growth factor-b (TGFb) signaling which is also influenced by various factors in the tumor microenvironment, and might contribute to lymphatic and distant metastasis [7, 37]."
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