RRC ID 12467
Author Tsukahara T, Tanno Y, Watanabe Y.
Title Phosphorylation of the CPC by Cdk1 promotes chromosome bi-orientation.
Journal Nature
Abstract 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.
Volume 467(7316)
Pages 719-23
Published 2010-10-7
DOI 10.1038/nature09390
PII nature09390
PMID 20739936
MeSH Amino Acid Sequence Animals Aurora Kinase B Aurora Kinases CDC2 Protein Kinase / metabolism* Carrier Proteins / genetics Carrier Proteins / metabolism Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism Cell Line Centromere / metabolism Chromosomal Proteins, Non-Histone / metabolism Chromosomes, Fungal / metabolism* Chromosomes, Human / metabolism* Cyclin B / genetics Cyclin B / metabolism Humans Inhibitor of Apoptosis Proteins Microtubule-Associated Proteins / metabolism Molecular Sequence Data Multiprotein Complexes / chemistry* Multiprotein Complexes / metabolism* Phosphorylation Protein Binding Protein-Serine-Threonine Kinases / genetics Protein-Serine-Threonine Kinases / metabolism Schizosaccharomyces / cytology Schizosaccharomyces / genetics Schizosaccharomyces / metabolism Schizosaccharomyces pombe Proteins / genetics Schizosaccharomyces pombe Proteins / metabolism* Substrate Specificity
IF 43.07
Times Cited 103
Yeast FY13725(PY615) FY13789(PZ917)