Ubiquitination and deubiquitination emerge as players in idiopathic pulmonary fibrosis pathogenesis and treatment

JCI Insight
Shuang LiYutong Zhao

Abstract

Idiopathic pulmonary fibrosis (IPF) is a fatal fibrotic lung disease that is associated with aberrant activation of TGF-β, myofibroblast differentiation, and abnormal extracellular matrix (ECM) production. Proper regulation of protein stability is important for maintenance of intracellular protein homeostasis and signaling. Ubiquitin E3 ligases mediate protein ubiquitination, and deubiquitinating enzymes (DUBs) reverse the process. The role of ubiquitin E3 ligases and DUBs in the pathogenesis of IPF is relatively unexplored. In this review, we provide an overview of how ubiquitin E3 ligases and DUBs modulate pulmonary fibrosis through regulation of both TGF-β-dependent and -independent pathways. We also summarize currently available small-molecule inhibitors of ubiquitin E3 ligases and DUBs as potential therapeutic strategies for the treatment of IPF.

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Citations

Sep 7, 2019·Journal of Cell Science·Jisca MajoléePeter L Hordijk
Feb 20, 2020·The Journal of Biological Chemistry·Travis B LearBill B Chen
Feb 13, 2020·International Journal of Molecular Sciences·Amina El AyadiAnesh Prasai
Jan 29, 2021·The Journal of Biological Chemistry·Travis B LearBill B Chen
Nov 28, 2020·Contemporary Clinical Trials·Lisa LancasterSteven D Nathan
Feb 23, 2021·Oral Diseases·Paramita KunduPaturu Kondaiah
Mar 6, 2021·Molecular Therapy. Nucleic Acids·Xi YangYonghong Li
Mar 5, 2021·Environmental Science and Pollution Research International·Amit GuptaSandeep Arora
May 1, 2021·Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver·Zhiyong DuCuifeng Wei
May 11, 2021·Respiratory Medicine and Research·I BaR Borie
May 26, 2021·Cell Biochemistry and Biophysics·Alyssa D GregoryYutong Zhao

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Methods Mentioned

BETA
ubiquitination
deubiquitination
sumoylation
bronchoalveolar lavage

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