2. Academic Validation
  3. Hsp70 and Hsp90 oppositely regulate TGF-β signaling through CHIP/Stub1

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

  • Biochem Biophys Res Commun. 2014 Mar 28;446(1):387-92. doi: 10.1016/j.bbrc.2014.02.124.
Yu Shang 1,  Xialian Xu 2,  Xiaolin Duan 3,  Junwei Guo 2,  Yinyin Wang 2,  Fangli Ren 2,  Dacheng He 4,  Zhijie Chang 5
Affiliations

Affiliations

  • 1 The Key Laboratory for Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing 100875, China; State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, Tsinghua University, Beijing 100084, China.
  • 2 State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, Tsinghua University, Beijing 100084, China.
  • 3 The Second People's Hospital of Zhuhai, Guangdong 519000, China.
  • 4 The Key Laboratory for Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing 100875, China.
  • 5 State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, Tsinghua University, Beijing 100084, China. Electronic address: [email protected].
PMID: 24613385 DOI: 10.1016/j.bbrc.2014.02.124
Abstract

Transforming Growth Factor-β (TGF-β) signaling plays an important role in regulation of a wide variety of cellular processes. Canonical TGF-β 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-β 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-β signaling. In contrast, over-expressed HSP90 antagonizes CHIP mediated SMAD3 ubiquitination and degradation and desensitizes cells in response to TGF-β signaling. Taken together, our data reveal an opposite role of HSP70 and HSP90 in regulating TGF-β signaling by implicating CHIP-mediated SMAD3 ubiquitination and degradation. This study provides a new insight into understanding the regulation of the TGF-β signaling by chaperones.

Keywords

CHIP/Stub1; Hsp70; Hsp90; Smad3 ubiquitination and degradation; TGF-β signal.

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