Meiling Zhao
Bo Yuan
Shuchen Gu
Mingjie Zheng
Jian Zou
Jianping Jin
Ting Liu
Xin-Hua Feng
aMOE Key Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou 310058, China
bDepartment of Biochemistry and Molecular Biology, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
cInstitute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou 310058, China
dDepartment of Cell Biology, School of Medicine, Zhejiang University, Hangzhou 310058, China
eDepartment of Molecular & Cellular Biology and Michael DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
More InformationCorresponding author: E-mail address: liuting518@zju.edu.cn (Ting Liu);E-mail address: fenglab@zju.edu.cn (Xin-Hua Feng)
Received Date: 2018-06-11
Accepted Date:2018-08-27
Rev Recd Date:2018-08-09
Available Online: 2018-11-27 Publish Date:2018-12-20
Abstract
Abstract
Smads are critical intracellular signal transducers for transforming growth factor-β (TGF-β) in mammalian cells. In this study, we have identified WD repeat-containing protein 74 (WDR74) as a novel transcriptional coactivator for Smads in the canonical TGF-β signaling pathway. Through direct interactions with Smad proteins, WDR74 enhances TGF-β-mediated phosphorylation and nuclear accumulation of Smad2 and Smad3. Consequently, WDR74 enables stronger transcriptional responses and more robust TGF-β-induced physiological responses. Our findings have elucidated a critical role of WDR74 in regulating TGF-β signaling.Keywords: WDR74,
TGF-β signaling,
Transcription,
Growth inhibition,
EMT
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