title: Phosphorylation of Ubc9 by Cdk1 enhances SUMOylation activity.
abstract: Increasing evidence has pointed to an important role of SUMOylation in cell cycle regulation, especially for M phase. In the current studies, we have obtained evidence through in vitro studies that the master M phase regulator CDK1/cyclin B kinase phosphorylates the SUMOylation machinery component Ubc9, leading to its enhanced SUMOylation activity. First, we show that CDK1/cyclin B, but not many other cell cycle kinases such as CDK2/cyclin E, ERK1, ERK2, PKA and JNK2/SAPK1, specifically enhances SUMOylation activity. Second, CDK1/cyclin B phosphorylates the SUMOylation machinery component Ubc9, but not SAE1/SAE2 or SUMO1. Third, CDK1/cyclin B-phosphorylated Ubc9 exhibits increased SUMOylation activity and elevated accumulation of the Ubc9-SUMO1 thioester conjugate. Fourth, CDK1/cyclin B enhances SUMOylation activity through phosphorylation of Ubc9 at serine 71. These studies demonstrate for the first time that the cell cycle-specific kinase CDK1/cyclin B phosphorylates a SUMOylation machinery component to increase its overall SUMOylation activity, suggesting that SUMOylation is part of the cell cycle program orchestrated by CDK1 through Ubc9.
authors.affiliation: Molecular and Cell Biology Program, Graduate Institute of Life Sciences, National Defense Medical Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Yee-Fun
authors.initials: YF
authors.lastname: Su
authors.forename: Tsunghan
authors.initials: T
authors.lastname: Yang
authors.forename: Hoting
authors.initials: H
authors.lastname: Huang
authors.forename: Leroy F
authors.initials: LF
authors.lastname: Liu
authors.forename: Jaulang
authors.initials: J
authors.lastname: Hwang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002453:Cell Cycle; D002460:Cell Line; D019926:Cyclin B / Q000378:metabolism; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D012694:Serine; D013379:Substrate Specificity; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000378:metabolism; D058207:Sumoylation; D044764:Ubiquitin-Activating Enzymes / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000737:chemistry / Q000378:metabolism*; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: D019926:Cyclin B; D013438:Sulfhydryl Compounds; D012694:Serine; D044763:Ubiquitin-Conjugating Enzymes; D016203:CDC2 Protein Kinase; D004264:DNA Topoisomerases, Type I; D044764:Ubiquitin-Activating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9