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Review
. 2020 Jun 4;21(11):4028.
doi: 10.3390/ijms21114028.

Regulation of Deubiquitinating Enzymes by Post-Translational Modifications

Tanuza Das  1 , Sang Chul Shin  1 , Eun Joo Song  2 , Eunice EunKyeong Kim  1
Affiliations
Review

Regulation of Deubiquitinating Enzymes by Post-Translational Modifications

Tanuza Das et al. Int J Mol Sci. .

Abstract

Ubiquitination and deubiquitination play a critical role in all aspects of cellular processes, and the enzymes involved are tightly regulated by multiple factors including posttranslational modifications like most other proteins. Dysfunction or misregulation of these enzymes could have dramatic physiological consequences, sometimes leading to diseases. Therefore, it is important to have a clear understanding of these regulatory processes. Here, we have reviewed the posttranslational modifications of deubiquitinating enzymes and their consequences on the catalytic activity, stability, abundance, localization, and interaction with the partner proteins.

Keywords: activity; deubiquitinase (DUB); deubiquitinating enzyme; disease; interaction; localization; post-translational modification (PTM).

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Diverse functions and regulations of deubiquitinating (or deubiquitylating) enzymes (DUBs). DUBs are grouped into seven categories based on their functions.
Figure 2
Figure 2
Post-translational modifications (PTMs)-mediated regulations on DUB.
Figure 3
Figure 3
Examples of phosphorylation on various DUBs. (a) Phosphorylation of USP37 in G1/S triggers its full DUB activity. Phospho-USP37 stabilizes cyclin A by removing degradative polyUb, whereas dephosphorylated USP37 can be ubiquitinated and undergoes proteasomal degradation in late mitosis [17]. (b) Phosphorylated USP10 translocates into the nucleus where it deubiquitinates p53 and inhibits Mdm2-induced p53 degradation [49]. (c) USP15 and USP4 dephosphorylation lead to their interaction with SART3, which in turn allows DUB translocation into the nucleus and the regulation of spliceosomal function [92]. (d) CK2-mediated phosphorylation stabilizes USP7, resulting in Mdm2 stabilization and p53 downregulation. USP7 dephosphorylation by PPM1G destabilizes USP7 resulting in Mdm2 degradation and upregulation of p53 [95].
Figure 4
Figure 4
Disease-related DUBs.
See this image and copyright information in PMC

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