RT Journal Article
SR Electronic
T1 Paradoxes of cellular SUMOylation regulation: a role of biomolecular condensates?
JF Pharmacological Reviews
JO Pharmacol Rev
FD American Society for Pharmacology and Experimental Therapeutics
SP PHARMREV-AR-2022-000784
DO 10.1124/pharmrev.122.000784
A1 Xiaodong Cheng
A1 Wenli Yang
A1 Wei Lin
A1 Fang Mei
YR 2023
UL http://pharmrev.aspetjournals.org/content/early/2023/05/03/pharmrev.122.000784.abstract
AB Protein SUMOylation is a major post-translational modification important for maintaining cellular homeostasis. SUMOylation has long been associated with stress responses as a diverse array of cellular stress signals are known to trigger rapid alternations in global protein SUMOylation. In addition, while there are large families of ubiquitination enzymes, all SUMOs are conjugated by a set of enzymatic machinery comprising one heterodimeric SUMO-activating enzyme, a single SUMO-conjugating enzyme, and a small number of SUMO protein ligases and SUMO-specific proteases. How a few SUMOylation enzymes specifically modify thousands of functional targets in response to diverse cellular stresses remains an enigma. Here, we review recent progress toward understanding the mechanisms of SUMO regulation, particularly, the potential roles of liquid-liquid phase separation/biomolecular condensates in the regulation of cellular SUMOylation during cellular stresses. In addition, we discuss the role of protein SUMOylation in pathogenesis and the development of novel therapeutics targeting SUMOylation. Significance Statement Protein SUMOylation is one of the most prevalent post-translational modifications and plays an important role in maintaining cellular homeostasis in response to stresses. Protein SUMOylation has been implicated in human pathogenesis such as cancer, cardiovascular diseases, neurodegeneration, and infection. After more than a quarter century of extensive research, intriguing enigmas remain regarding the mechanism of cellular SUMOylation regulation and the therapeutic potential of targeting SUMOylation.