Deubiquitylating Enzymes in Cancer and Immunity

Overview

Journal Adv Sci (Weinh)

Specialty Biomedical Engineering

Date 2023 Oct 27

PMID 37888853

Authors

Jiang Ren

Peng Yu

Sijia Liu

Ran Li

Xin Niu

Yan Chen

Zhenyu Zhang

Fangfang Zhou

Long Zhang

Affiliations

Soon will be listed here.

Abstract

Deubiquitylating enzymes (DUBs) maintain relative homeostasis of the cellular ubiquitome by removing the post-translational modification ubiquitin moiety from substrates. Numerous DUBs have been demonstrated specificity for cleaving a certain type of ubiquitin linkage or positions within ubiquitin chains. Moreover, several DUBs perform functions through specific protein-protein interactions in a catalytically independent manner, which further expands the versatility and complexity of DUBs' functions. Dysregulation of DUBs disrupts the dynamic equilibrium of ubiquitome and causes various diseases, especially cancer and immune disorders. This review summarizes the Janus-faced roles of DUBs in cancer including proteasomal degradation, DNA repair, apoptosis, and tumor metastasis, as well as in immunity involving innate immune receptor signaling and inflammatory and autoimmune disorders. The prospects and challenges for the clinical development of DUB inhibitors are further discussed. The review provides a comprehensive understanding of the multi-faced roles of DUBs in cancer and immunity.

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