SUMOylation modulates the function of Aurora-B kinase.
Aurora kinases are central regulators of mitotic-spindle assembly, chromosome segregation and cytokinesis. Aurora B is a member of the chromosomal passenger complex (CPC) with crucial functions in regulation of the attachment of kinetochores to microtubules and in cytokinesis. We report here that Aurora B contains a conserved SUMO modification motif within its kinase domain. Aurora B can bind SUMO peptides in vitro when bound to the IN-box domain of its CPC partner INCENP. Mutation of Lys207 to arginine (Aurora B(K207R)) impairs the formation of conjugates of Aurora B and SUMO in vivo. Expression of the SUMO-null form of Aurora B results in abnormal chromosome segregation and cytokinesis failure and it is not able to rescue mitotic defects in Aurora-B-knockout cells. These defects are accompanied by increased levels of the CPC on chromosome arms and defective centromeric function, as detected by decreased phosphorylation of the Aurora-B substrate CENP-A. The Aurora-B(K207R) mutant does not display reduced kinase activity, suggesting that functional defects are probably a consequence of the altered localization, rather than decreased intrinsic kinase activity. These data suggest that SUMOylation of Aurora B modulates its function, possibly by mediating the extraction of CPC complexes from chromosome arms during prometaphase.
Fernández-Miranda
Gonzalo
G
Cell Division and Cancer Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
Pérez de Castro
Ignacio
I
Carmena
Mar
M
Aguirre-Portolés
Cristina
C
Ruchaud
Sandrine
S
Fant
Xavier
X
Montoya
Guillermo
G
Earnshaw
William C
WC
Malumbres
Marcos
M
D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D018797:Cell Cycle Proteins / Q000378:metabolism; D002470:Cell Survival; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D020090:Chromosome Segregation; D048749:Cytokinesis / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D025842:SUMO-1 Protein / Q000378:metabolism*; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism; D058207:Sumoylation; D014162:Transfection
D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D025842:SUMO-1 Protein; C576921:AURKB protein, human; C576924:Aurkb protein, mouse; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases