USP7 Substrates Identified by Proteomics Analysis Reveal the Specificity of USP7

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2022 Oct 27

PMID 36302555

Authors

Litong Nie

Chao Wang

Xiaoguang Liu

Hongqi Teng

Siting Li

Min Huang

Xu Feng

Guangsheng Pei

Qinglei Hang

Zhongming Zhao

Boyi Gan

Li Ma

Junjie Chen

Affiliations

Soon will be listed here.

Abstract

Deubiquitylating enzymes (DUBs) remove ubiquitin chains from proteins and regulate protein stability and function. USP7 is one of the most extensively studied DUBs, since USP7 has several well-known substrates important for cancer progression, such as MDM2, N-MYC, and PTEN. Thus, USP7 is a promising drug target. However, systematic identification of USP7 substrates has not yet been performed. In this study, we carried out proteome profiling with label-free quantification in control and single/double-KO cells of and its closest homolog, Our proteome profiling for the first time revealed the proteome changes caused by and/or depletion. Combining protein profiling, transcriptome analysis, and tandem affinity purification of USP7-associated proteins, we compiled a list of 20 high-confidence USP7 substrates that includes known and novel USP7 substrates. We experimentally validated MGA and PHIP as new substrates of USP7. We further showed that MGA deletion reduced cell proliferation, similar to what was observed in cells with deletion. In conclusion, our proteome-wide analysis uncovered potential USP7 substrates, providing a resource for further functional studies.

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