title: Mitotic kinase Aurora-B is regulated by SUMO-2/3 conjugation/deconjugation during mitosis.
abstract: The small ubiquitin-related modifier (SUMO) system of higher eukaryotes plays important roles in normal cell division, especially in chromosome segregation. However, only a few mitotic SUMO substrates have been identified in mammals. Here, we show that the mitotic kinase Aurora-B can be modified by SUMO. The E3 SUMO-protein ligase PIAS3 [protein inhibitor of activated STAT (signal transducer and activator of transcription)] dramatically enhanced poly-SUMO-2/3 conjugation of Aurora-B, whereas the SUMO-specific isopeptidase SENP2 (Sentrin/SUMO-specific protease) specifically deconjugated SUMO from Aurora-B. The Lys-202 residue on human Aurora-B was preferentially modified by SUMO, and enhancement of SUMOylation in cells facilitated Aurora-B autophosphorylation, which is essential for its activation. Conversely, SENP2-mediated deSUMOylation of Aurora-B down-regulated its autophosphorylation in cells and also impaired its re-activation in Aurora inhibitor VX-680-treated mitotic cells. Poly-SUMO-2 conjugation of Aurora-B occurred during the M phase of the cell cycle, and both SUMO-2 and PIAS3 were localized adjacent to Aurora-B in the kinetochores in early mitosis. Based on these results, we propose that Aurora-B is a novel mitotic SUMO substrate and that its kinase activity is fine-tuned by the SUMO system.
authors.affiliation: Department of Biochemistry, Shimane University School of Medicine, Izumo 693-8501, Japan. banrei@med.shimane-u.ac.jp
authors.forename: Reiko
authors.initials: R
authors.lastname: Ban
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Nishida
authors.forename: Takeshi
authors.initials: T
authors.lastname: Urano
mesh_terms: D064107:Aurora Kinase B; D064127:Aurora Kinases; D001665:Binding Sites / Q000502:physiology; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D016193:G1 Phase / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis / Q000502:physiology*; D018832:Molecular Chaperones / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D011485:Protein Binding; D050828:Protein Inhibitors of Activated STAT / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D058207:Sumoylation / Q000502:physiology
chemical_list: D018832:Molecular Chaperones; C484745:PIAS3 protein, human; D050828:Protein Inhibitors of Activated STAT; D025841:Small Ubiquitin-Related Modifier Proteins; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D003546:Cysteine Endopeptidases; C501833:SENP2 protein, human