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Smad7 enables STAT3 activation and promotes pluripotency independent of TGF-ß signaling.
Yu, Yi; Gu, Shuchen; Li, Wenjian; Sun, Chuang; Chen, Fenfang; Xiao, Mu; Wang, Lei; Xu, Dewei; Li, Ye; Ding, Chen; Xia, Zongping; Li, Yi; Ye, Sheng; Xu, Pinglong; Zhao, Bin; Qin, Jun; Chen, Ye-Guang; Lin, Xia; Feng, Xin-Hua.
Affiliation
  • Yu Y; Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China.
  • Gu S; Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030.
  • Li W; Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China.
  • Sun C; Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China.
  • Chen F; Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030.
  • Xiao M; Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, TX 77030.
  • Wang L; Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030.
  • Xu D; Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China.
  • Li Y; Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China.
  • Ding C; Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China.
  • Xia Z; Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China.
  • Li Y; Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China.
  • Ye S; State Key Laboratory of Proteomics, Beijing Proteomics Research Center, Beijing 102206, China.
  • Xu P; State Key Laboratory of Genetic Engineering, College of Life Sciences, Fudan University, Shanghai 200032, China.
  • Zhao B; Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China.
  • Qin J; Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, TX 77030.
  • Chen YG; Baylor Breast Center, Baylor College of Medicine, Houston, TX 77030.
  • Lin X; Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China.
  • Feng XH; Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China.
Proc Natl Acad Sci U S A ; 114(38): 10113-10118, 2017 09 19.
Article in En | MEDLINE | ID: mdl-28874583
ABSTRACT
Smad7 is a negative feedback product of TGF-ß superfamily signaling and fine tunes a plethora of pleiotropic responses induced by TGF-ß ligands. However, its noncanonical functions independent of TGF-ß signaling remain to be elucidated. Here, we show that Smad7 activates signal transducers and activators of transcription 3 (STAT3) signaling in maintaining mouse embryonic stem cell pluripotency in a manner independent of the TGF-ß receptors, yet dependent on the leukemia inhibitory factor (LIF) coreceptor glycoprotein 130 (gp130). Smad7 directly binds to the intracellular domain of gp130 and disrupts the SHP2-gp130 or SOCS3-gp130 complex, thereby amplifying STAT3 activation. Consequently, Smad7 facilitates LIF-mediated self-renewal of mouse ESCs and is also critical for induced pluripotent stem cell reprogramming. This finding illustrates an uncovered role of the Smad7-STAT3 interplay in maintaining cell pluripotency and also implicates a mechanism involving Smad7 underlying cytokine-dependent regulation of cancer and inflammation.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Signal Transduction / Transforming Growth Factor beta / Smad7 Protein / STAT3 Transcription Factor / Mouse Embryonic Stem Cells Limits: Animals / Humans Language: En Journal: Proc Natl Acad Sci U S A Year: 2017 Type: Article Affiliation country: China
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Signal Transduction / Transforming Growth Factor beta / Smad7 Protein / STAT3 Transcription Factor / Mouse Embryonic Stem Cells Limits: Animals / Humans Language: En Journal: Proc Natl Acad Sci U S A Year: 2017 Type: Article Affiliation country: China