The role of deubiquitinating enzymes in apoptosis

Abstract

It has become apparent that ubiquitination plays a critical role in cell survival and cell death. In addition, deubiquitinating enzymes (DUBs) have been determined to be highly important regulators of these processes. Cells can be subjected to various stresses and respond in a variety of different ways ranging from activation of survival pathways to the promotion of cell death, which eventually eliminates damaged cells. The regulatory mechanisms of apoptosis depend on the balanced action between ubiquitination and deubiquitination systems. There is a growing recognition that DUBs play essential roles in regulating several binding partners to modulate the process of apoptosis. Thus, the interplay between the timing of DUB activity and the specificity of ubiquitin attachment and removal from its substrates during apoptosis is important to ensure cellular homeostasis. This review discusses the role of a few ubiquitin-specific DUBs that are involved in either promoting or suppressing the process of apoptosis.

The deubiquitinating enzyme DUBAI stabilizes DIAP1 to suppress Drosophila apoptosis

“…Accumulating evidence shows that DUBs tune various cellular pathways, including those governing cell survival and death. [28][29][30] To date, nearly 100 human proteins have been predicted to possess deubiquitinating activity. On the basis of their domain structure and peptide similarity, DUBs are subclassified into six families: ubiquitin-specific proteases (USPs), ubiquitin C-terminal hydrolases, ovarian tumor proteases (OTUs), Machado-Joseph disease protein domain proteases (Josephins), JAMM/MPN domain-associated metallopeptidases and monocyte chemotactic protein-induced protein.…”

Deubiquitinases in cancer: new functions and therapeutic options

“…CYLD has also been suggested to influence cell migration through the GTPase Rac1 (Gao et al, 2010). On the other hand, DUBs have dual and complex roles in the regulation of apoptotic processes, either promoting (USP2, USP7, USP8, USP9X, USP15, USP16, USP17, USP28, USP41, CYLD, UCHL1, A20 and ATXN3) or suppressing apoptosis (USP2, USP9X, USP18, UCHL3 and A20) (Vucic et al, 2011;Ramakrishna et al, 2011a). In an example of these dual functions, USP2 rescues prostate cancer cells from apoptosis by stabilizing fatty-acid synthase (Graner et al, 2004), and deubiquitylates and stabilizes the truncated form of the apoptosis-inducing factor AIF, thus promoting cell death (Oh et al, 2011).…”

Future Application of Deubiquitylating Enzymes for Rapid and Efficient Cellular Reprogramming

“…DUBs have been reported to recycle ubiquitin molecules, cleave polyubiquitin chains, process ubiquitin precursors and reverse ubiquitin conjugation [8]. Similar to ubiquitylation, DUBs are also involved in the regulation of numerous cellular activities such as proteasomedependent and lysosome-dependent proteolysis, DNA repair, gene expression, chromosome segregation, kinase activation, cell cycle progression, apoptosis, localization, spermatogenesis, and degradation of signaling intermediates [8,10,11].…”