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EPRS1 Controls the TGF-β Signaling Pathway via Interaction with TβRI in Hepatic Stellate Cell

Authors
 Ina Yoon  ;  Ji Ae Song  ;  Ji Hun Suh  ;  Sulhee Kim  ;  Jonghyeon Son  ;  Jong Hyun Kim  ;  Song Yee Jang  ;  Kwang Yeon Hwang  ;  Myung Hee Kim  ;  Sunghoon Kim 
Citation
 MOLECULAR AND CELLULAR BIOLOGY, Vol.43(5) : 223-240, 2023-05 
Journal Title
MOLECULAR AND CELLULAR BIOLOGY
ISSN
 0270-7306 
Issue Date
2023-05
MeSH
Fibrosis ; Hepatic Stellate Cells* / metabolism ; Humans ; Receptor, Transforming Growth Factor-beta Type I / metabolism ; Receptors, Transforming Growth Factor beta* / genetics ; Receptors, Transforming Growth Factor beta* / metabolism ; Signal Transduction / physiology ; Transforming Growth Factor beta / metabolism
Keywords
glutamyl-prolyl-tRNA synthetase 1 ; halofuginone ; transforming growth factor receptors
Abstract
Glutamyl-prolyl-tRNA synthetase 1 (EPRS1) is known to associated with fibrosis through its catalytic activity to produce prolyl-tRNA. Although its catalytic inhibitor halofuginone (HF) has been known to inhibit the TGF-beta pathway as well as to reduce prolyl-tRNA production for the control of fibrosis, the underlying mechanism how EPRS1 regulates the TGF-beta pathway was not fully understood. Here, we show a noncatalytic function of EPRS1 in controlling the TGF-beta pathway and hepatic stellate cell activation via its interaction with TGF-beta receptor I (T beta RI). Upon stimulation with TGF-beta, EPRS1 is phosphorylated by TGF-beta-activated kinase 1 (TAK1), leading to its dissociation from the multi-tRNA synthetase complex and subsequent binding with T beta RI. This interaction increases the association of T beta RI with SMAD2/3 while decreases that of T beta RI with SMAD7. Accordingly, EPRS1 stabilizes T beta RI by preventing the ubiquitin-mediated degradation of T beta RI. HF disrupts the interaction between EPRS1 and T beta RI, and reduces T beta RI protein levels, leading to inhibition of the TGF-beta pathway. In conclusion, this work suggests the novel function of EPRS1 involved in the development of fibrosis by regulating the TGF-beta pathway and the antifibrotic effects of HF by controlling both of EPRS1 functions.
Files in This Item:
T992023311.pdf Download
DOI
10.1080/10985549.2023.2205344
Appears in Collections:
1. College of Medicine (의과대학) > Others (기타) > 1. Journal Papers
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/199576
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