Ubiquitin-specific peptidase 37: an important cog in the oncogenic machinery of cancerous cells

Abstract

Protein ubiquitination is one of the most crucial posttranslational modifications responsible for regulating the stability and activity of proteins involved in homeostatic cellular function. Inconsistencies in the ubiquitination process may lead to tumorigenesis. Ubiquitin-specific peptidases are attractive therapeutic targets in different cancers and are being evaluated for clinical development. Ubiquitin-specific peptidase 37 (USP37) is one of the least studied members of the USP family. USP37 controls numerous aspects of oncogenesis, including stabilizing many different oncoproteins. Recent work highlights the role of USP37 in stimulating the epithelial-mesenchymal transition and metastasis in lung and breast cancer by stabilizing SNAI1 and stimulating the sonic hedgehog pathway, respectively. Several aspects of USP37 biology in cancer cells are yet unclear and are an active area of research. This review emphasizes the importance of USP37 in cancer and how identifying its molecular targets and signalling networks in various cancer types can help advance cancer therapeutics.

Ubiquitin specific peptidases and prostate cancer

“…Different USPs have specific substrate proteins; therefore, they can regulate different signaling pathways ( Ye et al, 2009 ). USPs can stabilize various oncoproteins or alter their cellular localization by deubiquitination, which can cause the development and progression of cancer ( Chauhan et al, 2021 ). Numerous studies have shown that targeting USPs might be a promising therapeutic approach for cancer treatment ( Dai et al, 2020 ; Du et al, 2021 ; Li et al, 2020 ; Ma et al, 2019 ; Nininahazwe et al, 2021 ; Zhu et al, 2020 ).…”

“…1 , ubiquitin can covalently conjugate to the substrate proteins by three different enzymes, including E1, E2, and E3, during ubiquitination ( Clague, Heride & Urbé, 2015 ). In eukaryotes, the ubiquitin-proteasome system, which is mainly composed of ubiquitin molecules, ubiquitylating enzymes, and 26S proteasomes, is an important pathway for the degradation of damaged or misfolded proteins ( Chauhan et al, 2021 ; Svikle et al, 2022 ).…”

USP21 contributes to the aggressiveness of laryngeal cancer cells by deubiquitinating and stabilizing AURKA

“…It is a reversible process and a key post‐translational modification, which is counter‐regulated by ubiquitinating enzymes and deubiquitinases 6,7 . Ubiquitination regulates protein stability and activity and is involved in homeostatic cellular functions 8 . By labeling proteins degraded by the proteasome, ubiquitination has always been considered a key determinant of protein fate 9 .…”

“…6,7 Ubiquitination regulates protein stability and activity and is involved in homeostatic cellular functions. 8 By labeling proteins degraded by the proteasome, ubiquitination has always been considered a key determinant of protein fate. 9 Deubiquitinases drive the cleavage of ubiquitin from substrates, which control the stability of most cellular proteins.…”

The multifaceted roles of cohesin in cancer

“…Cohesin dissociation from chromatin requires the activity of WAPL (Wings Apart-like Protein 1) which interacts directly with RAD21 and STAG1/2 [ 8 , 9 ]. Recently, it has been shown that WAPL is deubiquitinated by USP37 (Ubiquitin-specific peptidase 37) during mitosis, thereby regulating chromosomal segregation, cohesion and mitotic progression [ 10 , 11 ]. Finally, once chromosomes are correctly bioriented on the mitotic spindle at anaphase, cohesin is completely removed from chromosomes by the endopeptidase ESPL1 (Extra spindle pole bodies-like 1)/SEPARASE protein that cleaves RAD21 [ 12 , 13 ].…”