Mitotic kinase Aurora-B is regulated by SUMO-2/3 conjugation/deconjugation during mitosis.
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.
Mesh Terms:
Binding Sites, Cysteine Endopeptidases, Enzyme Activation, G1 Phase, Gene Expression Regulation, Enzymologic, HeLa Cells, Humans, Mitosis, Molecular Chaperones, Phosphorylation, Protein Binding, Protein Inhibitors of Activated STAT, Protein-Serine-Threonine Kinases, Small Ubiquitin-Related Modifier Proteins, Sumoylation
Binding Sites, Cysteine Endopeptidases, Enzyme Activation, G1 Phase, Gene Expression Regulation, Enzymologic, HeLa Cells, Humans, Mitosis, Molecular Chaperones, Phosphorylation, Protein Binding, Protein Inhibitors of Activated STAT, Protein-Serine-Threonine Kinases, Small Ubiquitin-Related Modifier Proteins, Sumoylation
Genes Cells
Date: Jun. 01, 2011
PubMed ID: 21554500
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