Chromosome alignment and segregation regulated by ubiquitination of survivin.
Proper chromosome segregation requires the attachment of sister kinetochores to microtubules from opposite spindle poles to form bi-oriented chromosomes on the metaphase spindle. The chromosome passenger complex containing Survivin and the kinase Aurora B regulates this process from the centromeres. We report that a de-ubiquitinating enzyme, hFAM, regulates chromosome alignment and segregation by controlling both the dynamic association of Survivin with centromeres and the proper targeting of Survivin and Aurora B to centromeres. Survivin is ubiquitinated in mitosis through both Lys(48) and Lys(63) ubiquitin linkages. Lys(63) de-ubiquitination mediated by hFAM is required for the dissociation of Survivin from centromeres, whereas Lys(63) ubiquitination mediated by the ubiquitin binding protein Ufd1 is required for the association of Survivin with centromeres. Thus, ubiquitinaton regulates dynamic protein-protein interactions and chromosome segregation independently of protein degradation.
Vong
Queenie P
QP
Department of Embryology, Carnegie Institution of Washington and Howard Hughes Medical Institute, 3520 San Martin Drive, Baltimore, MD 21218, USA.
Cao
Kan
K
Li
Hoi Y
HY
Iglesias
Pablo A
PA
Zheng
Yixian
Y
D000595:Amino Acid Sequence; D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D002503:Centromere / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D020090:Chromosome Segregation / Q000502:physiology*; D004527:Egg Proteins / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008239:Lysine / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000077022:Survivin; D025801:Ubiquitin / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase; D014981:Xenopus; D029867:Xenopus Proteins / Q000378:metabolism*
C107489:BIRC5 protein, human; D002868:Chromosomal Proteins, Non-Histone; D004527:Egg Proteins; C083767:INCENP protein, human; C513185:Incenp protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; C506234:USP9X protein, human; D025801:Ubiquitin; D029867:Xenopus Proteins; C472712:birc5.2 protein, Xenopus; C576921:AURKB protein, human; C576924:Aurkb protein, mouse; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D010450:Endopeptidases; D043222:Ubiquitin Thiolesterase; C506233:xFAM protein, Xenopus; D008239:Lysine