The oncogenic role of ubiquitin specific peptidase (USP8) and its signaling pathways targeting for cancer therapeutics

Md Tariqul Islam; Fangzhi Chen; Hanchun Chen

doi:10.1016/j.abb.2021.108811

The oncogenic role of ubiquitin specific peptidase (USP8) and its signaling pathways targeting for cancer therapeutics

Arch Biochem Biophys. 2021 Apr 15:701:108811. doi: 10.1016/j.abb.2021.108811. Epub 2021 Feb 16.

Authors

Md Tariqul Islam¹, Fangzhi Chen², Hanchun Chen³

Affiliations

¹ Department of Biochemistry and Molecular Biology, School of Life Sciences, Central South University, Changsha, China.
² Department of Urology, The Second Xiangya Hospital of Central South University, Changsha, China.
³ Department of Biochemistry and Molecular Biology, School of Life Sciences, Central South University, Changsha, China. Electronic address: chenhanchun@csu.edu.cn.

PMID: 33600786
DOI: 10.1016/j.abb.2021.108811

Abstract

USP8 is a deubiquitinating enzyme in the family of ubiquitin-specific proteases (USPs) which can remove ubiquitin from the substrate and protect the substrate from degradation. The upregulated or mutated USP8 becomes hyperactivated and stabilizes numerous oncogenes or proto-oncogenes leading to cancer progression and survival by activating multiple signaling pathways. Moreover, USP8 inhibition is also important to overcome anticancer drug-resistant. This review is the first study to find, combine, analyze, and represent the multiple oncogenic signaling pathways with their downstream and upstream regulation activated or enhanced by USP8, which will help the researchers to find any therapeutic strategy for drug discovery by inhibiting or suppressing the multi-targeted USP8.

Keywords: Cancer therapeutics; Deubiquitination; EGFR; Signaling pathway; USP8.

Publication types

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

MeSH terms

Antineoplastic Agents / therapeutic use*
Drug Discovery
Drug Resistance, Neoplasm / drug effects*
Drug Resistance, Neoplasm / genetics
Endopeptidases* / genetics
Endopeptidases* / metabolism
Endosomal Sorting Complexes Required for Transport* / antagonists & inhibitors
Endosomal Sorting Complexes Required for Transport* / genetics
Endosomal Sorting Complexes Required for Transport* / metabolism
Humans
Neoplasms / drug therapy*
Neoplasms / genetics
Neoplasms / metabolism*
Neoplasms / pathology
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins / metabolism*
Signal Transduction / drug effects*
Signal Transduction / genetics
Ubiquitin / genetics
Ubiquitin / metabolism
Ubiquitin Thiolesterase* / antagonists & inhibitors
Ubiquitin Thiolesterase* / genetics
Ubiquitin Thiolesterase* / metabolism

Substances

Antineoplastic Agents
Endosomal Sorting Complexes Required for Transport
Proto-Oncogene Proteins
Ubiquitin
Endopeptidases
USP8 protein, human
Ubiquitin Thiolesterase