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.

Fig. 1

The ubiquitin proteolytic pathway (UPP). The process of ubiquitination is regulated by organized milieu of E1, E2 and E3 enzymes, which mediate the ligation of ubiquitin to the lysine residues in proteins targeted to the 26S proteasome for degradation. Ubiquitins are recycled by the action of DUB enzymes

Fig. 2

Schematic overview of DUBs involved in the process of cell death by regulating its substrates. Activities involved in the inhibition of apoptosis are represented with lines ending in a ‘T’ symbol. Activities involved in inducing apoptosis are represented with arrowheads. USP family proteins are represented in blue, UCH family proteins are represented in yellow, and ataxin family proteins are represented in green. A detailed explanation of the figure is given in the text