Leiden University Scholarly Publications

Vertegaal, A.C.O. (2022)

Signalling mechanisms and cellular functions of SUMO

Article / Letter to editor

Sumoylation regulates thousands of proteins, many of which are nuclear. Recent studies have implicated sumoylation in liquid-liquid phase separation and assembly of nuclear bodies, and have uncovered its roles in immunity and pluripotency and links to disease, thereby opening new therapeutic avenues.Sumoylation is an essential post-translational modification that is catalysed by a small number of modifying enzymes but regulates thousands of target proteins in a dynamic manner. Small ubiquitin-like modifiers (SUMOs) can be attached to target proteins as one or more monomers or in the form of polymers of different types. Non-covalent readers recognize SUMO-modified proteins via SUMO interaction motifs. SUMO simultaneously modifies groups of functionally related proteins to regulate predominantly nuclear processes, including gene expression, the DNA damage response, RNA processing, cell cycle progression and proteostasis. Recent progress has increased our understanding of the cellular...Show moreSumoylation regulates thousands of proteins, many of which are nuclear. Recent studies have implicated sumoylation in liquid-liquid phase separation and assembly of nuclear bodies, and have uncovered its roles in immunity and pluripotency and links to disease, thereby opening new therapeutic avenues.Sumoylation is an essential post-translational modification that is catalysed by a small number of modifying enzymes but regulates thousands of target proteins in a dynamic manner. Small ubiquitin-like modifiers (SUMOs) can be attached to target proteins as one or more monomers or in the form of polymers of different types. Non-covalent readers recognize SUMO-modified proteins via SUMO interaction motifs. SUMO simultaneously modifies groups of functionally related proteins to regulate predominantly nuclear processes, including gene expression, the DNA damage response, RNA processing, cell cycle progression and proteostasis. Recent progress has increased our understanding of the cellular and pathophysiological roles of SUMO modifications, extending their functions to the regulation of immunity, pluripotency and nuclear body assembly in response to oxidative stress, which partly occurs through the recently characterized mechanism of liquid-liquid phase separation. Such progress in understanding the roles and regulation of sumoylation opens new avenues for the targeting of SUMO to treat disease, and indeed the first drug blocking sumoylation is currently under investigation in clinical trials as a possible anticancer agent.Show less

All authors

Vertegaal, A.C.O.

Date

2022-06-24

Journal

Nature Reviews Molecular Cell Biology

Volume

23

Issue

11

Pages

715 - 731

DOI

doi:10.1038/s41580-022-00500-y