Medicine and Health

USP18 is an essential regulator of muscle cell differentiation and maturation

C. S. Olie, A. Pinto-fernández, et al.

This groundbreaking study by Cyriel Sebastiaan Olie and colleagues uncovers the pivotal role of ubiquitin-specific protease 18 (USP18) in muscle cell differentiation. It reveals how USP18 influences both the initiation and maintenance of muscle cell formation, independent of its immune response role. Delve into the intricate relationship between gene expression and muscle physiology, as this research opens new avenues for understanding muscle pathologies.

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Playback language: English

Index

Abstract

The ubiquitin proteasomal system (UPS) is crucial for muscle physiology, and UPS impairment is implicated in many muscle pathologies. This study investigated the role of deubiquitinating enzymes (DUBs) in muscle cell differentiation. A genetic screen revealed that ubiquitin-specific protease 18 (USP18) depletion initially stimulated differentiation but later impaired myotube maintenance. Surprisingly, USP18's function in muscle cells is independent of its known role in attenuating the immune response via interferon-stimulated gene 15 (ISG15) removal. USP18 depletion altered gene expression, affecting cell cycle genes, myogenic transcription factors, and calcium channel networks. This resulted in reduced calcium flux and contractile force in engineered muscle models. Nuclear USP18 is identified as a critical regulator of both differentiation initiation and maintenance, independent of its canonical ISG15-related function.

Publisher

Cell Death and Disease

Published On

Mar 31, 2023

Authors

Cyriel Sebastiaan Olie, Adán Pinto-Fernández, Andreas Damianou, Iolanda Vendrell, Hailiang Mei, Bianca den Hamer, Erik van der Wal, Jessica C. de Greef, Vered Raz, Benedikt M. Kessler

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