UBC9 autosumoylation negatively regulates sumoylation of septins in Saccharomyces cerevisiae

Sumoylation regulates a wide range of cellular processes. However, little is known about the regulation of the SUMO machinery. In this study, we demonstrate that two lysine residues (Lys-153 and Lys-157) in the C-terminal region of the yeast E2-conjugating enzyme Ubc9 are the major and minor autosumoylation sites, respectively. Surprisingly, mutation of Lys-157 (ubc9^K157R) significantly stimulates the level of Ubc9 autosumoylation at Lys-153. The functional role of Ubc9 autosumoylation is exemplified in our findings that cell cycle-dependent sumoylation of cytoskeletal septin proteins is inversely correlated with the Ubc9 autosumoylation level and that mutation of the Ubc9 autosumoylation sites results in aberrant cell morphology. Our study elucidates a regulatory mechanism that utilizes automodification of the E2 enzyme of the sumoylation machinery to control substrate sumoylation.