Phosphorylation of the CPC by Cdk1 promotes chromosome bi-orientation

• Published in: Nature (London) 2010-10, Vol.467 (7316), p.719-723
• Main Authors: Watanabe, Yoshinori, Tsukahara, Tatsuya, Tanno, Yuji
• Format: Article
• Language: English
• Subjects: 631/208; 631/337/641; 631/80/458/1733; Amino Acid Sequence; Animals; Aurora Kinase B; Aurora Kinases; Biological and medical sciences; Carrier Proteins - genetics; Carrier Proteins - metabolism; CDC2 Protein Kinase - metabolism; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell cycle, cell proliferation; Cell division; Cell Line; Cell physiology; Centromere - metabolism; Chromosomal Proteins, Non-Histone - metabolism; Chromosomes; Chromosomes, Fungal - metabolism; Chromosomes, Human - metabolism; Cyclin B - genetics; Cyclin B - metabolism; Fundamental and applied biological sciences. Psychology; Genetic aspects; Genetic regulation; Humanities and Social Sciences; Humans; Inhibitor of Apoptosis Proteins; letter; Microtubule-Associated Proteins - metabolism; Molecular and cellular biology; Molecular Sequence Data; multidisciplinary; Multiprotein Complexes - chemistry; Multiprotein Complexes - metabolism; Mutation; Phosphorylation; Phosphotransferases; Physiological aspects; Protein Binding; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Proteins; Relocation; Schizosaccharomyces - cytology; Schizosaccharomyces - genetics; Schizosaccharomyces - metabolism; Schizosaccharomyces pombe; Schizosaccharomyces pombe Proteins - genetics; Schizosaccharomyces pombe Proteins - metabolism; Science; Science (multidisciplinary); Substrate Specificity; Survivin; Yeasts
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature09390

Successful partition of replicated genomes at cell division requires chromosome attachment to opposite poles of mitotic spindle (bi-orientation). Any defects in this regulation bring about chromosomal instability, which may accelerate tumour progression in humans. To achieve chromosome bi-orientation at prometaphase, the chromosomal passenger complex (CPC), composed of catalytic kinase Aurora B and regulatory components (INCENP, Survivin and Borealin), must be localized to centromeres to phosphorylate kinetochore substrates. Although the CPC dynamically changes the subcellular localization, the regulation of centromere targeting is largely unknown. Here we isolated a fission yeast cyclin B mutant defective specifically in chromosome bi-orientation. Accordingly, we identified Cdk1 (also known as Cdc2)-cyclin-B-dependent phosphorylation of Survivin. Preventing Survivin phosphorylation impairs centromere CPC targeting as well as chromosome bi-orientation, whereas phosphomimetic Survivin suppresses the bi-orientation defect in the cyclin B mutant. Survivin phosphorylation promotes direct binding with shugoshin, which we now define as a conserved centromeric adaptor of the CPC. In human cells, the phosphorylation of Borealin has a comparable role. Thus, our study resolves the conserved mechanisms of CPC targeting to centromeres, highlighting a key role of Cdk1-cyclin B in chromosome bi-orientation.