WDR74 functions as a novel coactivator in TGF-β signaling

Jinquan Liu; Meiling Zhao; Bo Yuan; Shuchen Gu; Mingjie Zheng; Jian Zou; Jianping Jin; Ting Liu; Xin-Hua Feng

doi:10.1016/j.jgg.2018.08.005

WDR74 functions as a novel coactivator in TGF-β signaling

J Genet Genomics. 2018 Dec 20;45(12):639-650. doi: 10.1016/j.jgg.2018.08.005. Epub 2018 Nov 27.

Authors

Jinquan Liu¹, Meiling Zhao², Bo Yuan², Shuchen Gu², Mingjie Zheng³, Jian Zou⁴, Jianping Jin⁵, Ting Liu⁶, Xin-Hua Feng⁷

Affiliations

¹ MOE Key Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou 310058, China; Department of Biochemistry and Molecular Biology, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
² MOE Key Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou 310058, China.
³ MOE Key Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou 310058, China; Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou 310058, China.
⁴ Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou 310058, China.
⁵ Department of Biochemistry and Molecular Biology, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
⁶ MOE Key Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou 310058, China; Department of Cell Biology, School of Medicine, Zhejiang University, Hangzhou 310058, China. Electronic address: liuting518@zju.edu.cn.
⁷ MOE Key Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou 310058, China; Department of Molecular & Cellular Biology and Michael DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: fenglab@zju.edu.cn.

PMID: 30594465
DOI: 10.1016/j.jgg.2018.08.005

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: EMT; Growth inhibition; TGF-β signaling; Transcription; WDR74.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carrier Proteins / genetics
Carrier Proteins / metabolism*
Cell Nucleus / genetics
Cell Nucleus / metabolism
Humans
Phosphorylation
Protein Binding
Protein Transport
RNA-Binding Proteins
Signal Transduction
Smad2 Protein / genetics
Smad2 Protein / metabolism
Smad3 Protein / genetics
Smad3 Protein / metabolism
Transcription, Genetic
Transforming Growth Factor beta / genetics
Transforming Growth Factor beta / metabolism*

Substances

Carrier Proteins
RNA-Binding Proteins
SMAD2 protein, human
SMAD3 protein, human
Smad2 Protein
Smad3 Protein
Transforming Growth Factor beta
WDR74 protein, human