Modification of the SUMO activating enzyme subunit SAE2 directs SUMO isoform bias required for mitotic fidelity

Abstract

AbstractProtein conjugation with the Small Ubiquitin-like Modifier SUMO1 or the related SUMO2/3 drive changes to protein behaviour. Many substrates are found modified by both SUMO1 and SUMO2/3, while others are modified by one or the other. How isoform specificity is directed is poorly understood. Here we examine modification of the catalytic component of the human SUMO Activation Enzyme, SAE2. We find that an acetylated K164-SAE2 analogue preferentially activates SUMO2 in competition with SUMO1, and that K164-SAE2 discriminates paralogues through their C-terminal regions. We find that K164-SAE2 is deacetylated during mitosis. Mitotic defects in cells expressing an acetylated K164-SAE2 analogue can be corrected by over-expression of SUMO1, suggesting SUMO1 conjugation driven by the deacetylated enzyme supports mitotic fidelity. These surprising data reveal that modification of the SUMO-activating enzyme can bias SUMO paralogue conjugation.