Frontiers in Pharmacology (Aug 2020)

Machado-Joseph Deubiquitinases: From Cellular Functions to Potential Therapy Targets

  • Chenming Zeng,
  • Chenxi Zhao,
  • Fujing Ge,
  • Yuekang Li,
  • Ji Cao,
  • Meidan Ying,
  • Jinjian Lu,
  • Qiaojun He,
  • Bo Yang,
  • Xiaoyang Dai,
  • Hong Zhu

DOI
https://doi.org/10.3389/fphar.2020.01311
Journal volume & issue
Vol. 11

Abstract

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Ubiquitination is known as important post-translational modification in cancer-related pathways. Human deubiquitinases (DUBs), with functions of modulating the ubiquitination process, are a family with about 100 proteins. They mainly function by cutting ubiquitin chains of the substrates. The Machado-Joseph domain-containing proteases (MJDs) is one of the sub-families of DUBs, consisting of four members, namely, Ataxin-3, Ataxin-3L, JOSD1, and JOSD2. Recent studies have provided new insights into biological functions of MJDs in the progression of Machado-Joseph disease or cancer diseases. In this review, we summarized the cellular functions and regulatory mechanisms of MJDs in Machado-Joseph disease and cancer pathways. Furthermore, we summarized MJDs genetic alterations in different human cancers by exploring the public databases (cBioportal). The aim of this review is to provide a comprehensive account based on our current knowledge about emerging insights into MJDs in physiology and disease, which might shed light on fundamental biological questions and promise to provide a potential target for therapeutic intervention.

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