Jab1/CSN5是COP9信号体的一个组成部分，通过与Smad7结合并促进其降解来调节转化生长因子β信号通路。
Jab1/CSN5, a component of the COP9 signalosome, regulates transforming growth factor beta signaling by binding to Smad7 and promoting its degradation.
作者信息
Kim Byung-Chul, Lee Ho-Jae, Park Seok Hee, Lee Sae Ra, Karpova Tatiana S, McNally James G, Felici Angelina, Lee Dug Keun, Kim Seong-Jin
机构信息
Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-5055, USA.
出版信息
Mol Cell Biol. 2004 Mar;24(6):2251-62. doi: 10.1128/MCB.24.6.2251-2262.2004.
Smad7 inhibits responses mediated by transforming growth factor beta (TGF-beta) and acts in a negative-feedback loop to regulate the intensity or duration of the TGF-beta signal. However, the aberrant expression and continued presence of Smad7 may cause TGF-beta resistance. Here we report that Jab1/CSN5, which is a component of the COP9 signalosome complex, associates constitutively with Smad7 and that overexpression of Jab1/CSN5 causes the translocation of Smad7 from the nucleus to the cytoplasm, promoting its degradation. Overexpression of Jab1/CSN5 increases Smad2 phosphorylation and enhances TGF-beta-induced transcriptional activity. The inhibition of endogenous Jab1/CSN5 expression by small interfering RNA (siRNA) induces Smad7 expression. This study thus defines Jab1/CSN5 as an adapter that targets Smad7 for degradation, thus releasing Smad7-mediated suppression of TGF-beta signaling.
Smad7抑制由转化生长因子β（TGF-β）介导的反应，并在负反馈回路中发挥作用，以调节TGF-β信号的强度或持续时间。然而，Smad7的异常表达和持续存在可能导致TGF-β抵抗。在此我们报告，COP9信号体复合物的一个组分Jab1/CSN5与Smad7组成性结合，并且Jab1/CSN5的过表达导致Smad7从细胞核易位至细胞质，促进其降解。Jab1/CSN5的过表达增加Smad2磷酸化并增强TGF-β诱导的转录活性。小干扰RNA（siRNA）对内源性Jab1/CSN5表达的抑制诱导Smad7表达。因此，本研究将Jab1/CSN5定义为一种衔接蛋白，其靶向Smad7进行降解，从而解除Smad7介导的对TGF-β信号传导的抑制。
Zotero 插件