Quantitative analyses of the metaphase-to-anaphase transition reveal differential kinetic regulation for securin and cyclin B1

Makoto Konishi, Norihisa Shindo, Masataka Komiya, Kozo Tanaka, Takehiko Itoh, Toru Hirota

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Separation of sister chromatids is a drastic and irreversible step in the cell cycle. The key biochemistry behind this event is the proteolysis mediated by the ubiquitin ligase called the anaphase promoting complex, or APC/C. Securin and cyclin B1 are the two established substrates for APC/ C whose degradation releases separase and inactivates cyclin B1-dependent kinase 1 (cdk1), respectively, at the metaphase-to-anaphase transition. In this study, we have combined biochemical quantifications with mathematical simulations to characterize the kinetic regulation of securin and cyclin B1, in the cytoplasmic and chromosomal compartments, and found that they are differentially distributed and degraded with different rates. Modeling their interaction with separase predicted that activation timing of separase well coincides with the decline of securin-separase concentration in the cytoplasm. Notably, it also coincides with the peak of cyclin B1-separase level on chromosomes, which appeared crucial to coordinate the timing for separase activation and cdk1 inhibition. We have also conducted phosphoproteomic analysis and identified Ki67 as a chromosomal cdk1 substrate whose dephosphorylation is facilitated by cyclin B1-separase interaction in anaphase.

Original languageEnglish
Pages (from-to)75-85
Number of pages11
JournalBiomedical Research (Japan)
Volume39
Issue number2
DOIs
Publication statusPublished - 2018

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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