title: Small ubiquitin-like modifier (SUMO) modification of E1 Cys domain inhibits E1 Cys domain enzymatic activity.
abstract: Although it is well established that ubiquitin-like modifications are tightly regulated, it has been unclear how their E1 activities are controlled. In this study, we found that the SAE2 subunit of the small ubiquitin-like modifier (SUMO) E1 is autoSUMOylated at residue Lys-236, and SUMOylation was catalyzed by Ubc9 at several additional Lys residues surrounding the catalytic Cys-173 of SAE2. AutoSUMOylation of SAE2 did not affect SUMO adenylation or formation of E1·SUMO thioester, but did significantly inhibit the transfer of SUMO from E1 to E2 and overall SUMO conjugations to target proteins due to the altered interaction between E1 and E2. Upon heat shock, SUMOylation of SAE2 was reduced, which corresponded with an increase in global SUMOylation, suggesting that SUMOylation of the Cys domain of SAE2 is a mechanism for "storing" a pool of E1 that can be quickly activated in response to environmental changes. This study is the first to show how E1 activity is controlled by post-translational modifications, and similar regulation likely exists across the homologous E1s of ubiquitin-like modifications.
authors.affiliation: Department of Molecular Medicine, Beckman Research Institute of the City of Hope, Duarte, California 91010, USA.
authors.forename: Khue
authors.initials: K
authors.lastname: Truong
authors.forename: Terry D
authors.initials: TD
authors.lastname: Lee
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chen
mesh_terms: D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D003545:Cysteine / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D009154:Mutation; D011485:Protein Binding; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism*; D058207:Sumoylation; D014162:Transfection; D044764:Ubiquitin-Activating Enzymes / Q000235:genetics / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism*; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: D025842:SUMO-1 Protein; C495501:SUMO1 protein, human; C470301:UBA2 protein, human; D044763:Ubiquitin-Conjugating Enzymes; C470299:SAE1 protein, human; D044764:Ubiquitin-Activating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9; D003545:Cysteine