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

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

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

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-β pathway as well as to reduce prolyl-tRNA production for the control of fibrosis, the underlying mechanism how EPRS1 regulates the TGF-β pathway was not fully understood. Here, we show a noncatalytic function of EPRS1 in controlling the TGF-β pathway and hepatic stellate cell activation via its interaction with TGF-β receptor I (TβRI). Upon stimulation with TGF-β, EPRS1 is phosphorylated by TGF-β-activated kinase 1 (TAK1), leading to its dissociation from the multi-tRNA synthetase complex and subsequent binding with TβRI. This interaction increases the association of TβRI with SMAD2/3 while decreases that of TβRI with SMAD7. Accordingly, EPRS1 stabilizes TβRI by preventing the ubiquitin-mediated degradation of TβRI. HF disrupts the interaction between EPRS1 and TβRI, and reduces TβRI protein levels, leading to inhibition of the TGF-β pathway. In conclusion, this work suggests the novel function of EPRS1 involved in the development of fibrosis by regulating the TGF-β pathway and the antifibrotic effects of HF by controlling both of EPRS1 functions.

Original languageEnglish
Pages (from-to)223-240
Number of pages18
JournalMolecular and cellular biology
Volume43
Issue number5
DOIs
Publication statusPublished - 2023

Bibliographical note

Publisher Copyright:
© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.

Keywords

  • glutamyl-prolyl-tRNA synthetase 1
  • halofuginone
  • transforming growth factor receptors

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'EPRS1 Controls the TGF-β Signaling Pathway via Interaction with TβRI in Hepatic Stellate Cell'. Together they form a unique fingerprint.

Cite this