Current and future directions of USP7 interactome in cancer study

Hong-Beom Park, Kwang-Hyun Baek

Biochim Biophys Acta Rev Cancer. 2023 Sep 27;1878(6):188992. doi: 10.1016/j.bbcan.2023.188992.

[Abstract]
The ubiquitin-proteasome system (UPS) is an essential protein quality controller for regulating protein homeostasis and autophagy. Ubiquitination is a protein modification process that involves the binding of one or more ubiquitins to substrates through a series of enzymatic processes. These include ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), and ubiquitin ligases (E3). Conversely, deubiquitination is a reverse process that removes ubiquitin from substrates via deubiquitinating enzymes (DUBs). Dysregulation of ubiquitination-related enzymes can lead to various human diseases, including cancer, through the modulation of protein ubiquitination. The most structurally and functionally studied DUB is the ubiquitin-specific protease 7 (USP7). Both the TRAF and UBL domains of USP7 are known to bind to the [P/A/E]-X-X-S or K-X-X-X-K motif of substrates. USP7 has been shown to be involved in cancer pathogenesis by binding with numerous substrates. Recently, a novel substrate of USP7 was discovered through a systemic analysis of its binding motif. This review summarizes the currently discovered substrates and cellular functions of USP7 in cancer and suggests putative substrates of USP7 through a comprehensive systemic analysis.

[Keywords]
Binding motif; Bioinformatics; Deubiquitination; Substrates; Ubiquitin-specific protease 7.

PMID : 37775071
Fulltext : https://www.sciencedirect.com/science/article/pii/S0304419X23001415?via%3Dihub