Hsp70 and Hsp90 oppositely regulate TGF-尾 signaling through CHIP/Stub1

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• 作者：Yu Shang^a ; ^b ; ¹ ; Xialian Xu^b ; ¹ ; Xiaolin Duan^c ; Junwei Guo^b ; Yinyin Wang^b ; Fangli Ren^b ; Dacheng He^a ; Zhijie Chang^b ; ^{zhijiec@tsinghua.edu.cn" class="auth_mail}
• 关键词：CHIP/Stub1 ; Smad3 ubiquitination and degradation ; Hsp70 ; Hsp90 ; TGF-尾 signal
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：28 March, 2014
• 年：2014
• 卷：446
• 期：1
• 页码：387-392
• 全文大小：914 K

文摘

Transforming growth factor-尾 (TGF-尾) signaling plays an important role in regulation of a wide variety of cellular processes. Canonical TGF-尾 signaling is mediated by Smads which were further regulated by several factors. We previously reported that E3 ubiquitin ligase CHIP (carboxyl terminus of Hsc70-interacting protein, also named Stub1) controlled the sensitivity of TGF-尾 signaling by modulating the basal level of Smad3 through ubiquitin-mediated degradation. Here, we present evidence that Hsp70 and Hsp90 regulate the complex formation of Smad3/CHIP. Furthermore, we observed that over-expressed Hsp70 or inhibition of Hsp90 by geldanamycin (GA) leads to facilitated CHIP-induced ubiquitination and degradation of Smad3, which finally enhances TGF-尾 signaling. In contrast, over-expressed Hsp90 antagonizes CHIP mediated Smad3 ubiquitination and degradation and desensitizes cells in response to TGF-尾 signaling. Taken together, our data reveal an opposite role of Hsp70 and Hsp90 in regulating TGF-尾 signaling by implicating CHIP-mediated Smad3 ubiquitination and degradation. This study provides a new insight into understanding the regulation of the TGF-尾 signaling by chaperones.