Structural and Functional Basis of JAMM Deubiquitinating Enzymes in Disease

Xin Pan; Sihua Wu; Wenping Wei; Zixuan Chen; Yong Wu; Kaizheng Gong

doi:10.3390/biom12070910

Structural and Functional Basis of JAMM Deubiquitinating Enzymes in Disease

Biomolecules. 2022 Jun 29;12(7):910. doi: 10.3390/biom12070910.

Authors

Xin Pan¹, Sihua Wu^{2

3}, Wenping Wei¹, Zixuan Chen¹, Yong Wu¹, Kaizheng Gong¹

Affiliations

¹ Department of Cardiology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou 225000, China.
² State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100864, China.
³ Division of Molecular Science, Graduate School of Science and Technology, Gunma University, Kiryu 376-8515, Gunma, Japan.

Abstract

Deubiquitinating enzymes (DUBs) are a group of proteases that are important for maintaining cell homeostasis by regulating the balance between ubiquitination and deubiquitination. As the only known metalloproteinase family of DUBs, JAB1/MPN/Mov34 metalloenzymes (JAMMs) are specifically associated with tumorigenesis and immunological and inflammatory diseases at multiple levels. The far smaller numbers and distinct catalytic mechanism of JAMMs render them attractive drug targets. Currently, several JAMM inhibitors have been successfully developed and have shown promising therapeutic efficacy. To gain greater insight into JAMMs, in this review, we focus on several key proteins in this family, including AMSH, AMSH-LP, BRCC36, Rpn11, and CSN5, and emphatically discuss their structural basis, diverse functions, catalytic mechanism, and current reported inhibitors targeting JAMMs. These advances set the stage for the exploitation of JAMMs as a target for the treatment of various diseases.

Keywords: JAMMs; catalytic mechanism; deubiquitinating enzymes; functions; inhibitors; structural basis.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Deubiquitinating Enzymes
Endopeptidases*
Peptide Hydrolases*
Proteins
Ubiquitination

Substances

Proteins
Endopeptidases
Peptide Hydrolases
Deubiquitinating Enzymes

Grants and funding

This work was financially supported by the National Natural Science Foundation of China (81970225; 82000257), the Natural Science Foundation of Jiangsu Higher Education Institutions of China (20KJB320006), Scientific Research Topics of Jiangsu Provincial Health Commission (M2021076), the Social Development Project of Yangzhou City (YZ2020087) and the Young Talent Support Project of Jiangsu Provincial Association for Science and Technology.