Wrestling with stress: roles of protein SUMOylation and deSUMOylation in cell stress response

Abstract

How cell fate is determined following extreme stress is a core question in cell biology. This is particularly important in the brain where neuronal death following ischemic stroke is a major cause of disability. Over the last few years it has emerged that the SUMOylation status of an increasing number of substrate proteins plays a crucial role in cellular responses to environmental and metabolic stress. SUMOylation is a post-translational modification in which the 97-residue protein, SUMO (Small Ubiquitin-related MOdifier) is covalently attached to specific lysine residues in a target protein. Despite being covalent, it is a highly transient modification because of the actions of deSUMOylation enzymes, so SUMO conjugation acts as a rapidly reversible switch that can promote or inhibit protein interactions with the substrate protein. Overall, it appears that increased SUMOylation represents a cellular protective response. Here we discuss recent progress toward understanding the mechanisms, pathways, and roles of SUMOylation during and after severe metabolic stress.

Keywords: SENP; SUMO; cell death; cell stress; cell survival; posttranslational modification; proteases.