Cdc20 hypomorphic mice fail to counteract de novo synthesis of cyclin B1 in mitosis

Liviu Malureanu, Karthik B. Jeganathan, Fang Jin, Darren J. Baker, Janine H. Van Ree, Oliver Gullon, Zheyan Chen, John R. Henley, Jan M. Van Deursen

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Cdc20 is an activator of the anaphase-promoting complex/cyclosome that initiates anaphase onset by ordering the destruction of cyclin B1 and securin in metaphase. To study the physiological significance of Cdc20 in higher eukaryotes, we generated hypomorphic mice that express small amounts of this essential cell cycle regulator. In this study, we show that these mice are healthy and not prone to cancer despite substantial aneuploidy. Cdc20 hypomorphism causes chromatin bridging and chromosome misalignment, revealing a requirement for Cdc20 in efficient sister chromosome separation and chromosome-microtubule attachment. We find that cyclin B1 is newly synthesized during mitosis via cytoplasmic polyadenylation element-binding protein-dependent translation, causing its rapid accumulation between prometaphase and metaphase of Cdc20 hypomorphic cells. Anaphase onset is significantly delayed in Cdc20 hypomorphic cells but not when translation is inhibited during mitosis. These data reveal that Cdc20 is particularly rate limiting for cyclin B1 destruction because of regulated de novo synthesis of this cyclin after prometaphase onset.

Original languageEnglish (US)
Pages (from-to)313-329
Number of pages17
JournalJournal of Cell Biology
Volume191
Issue number2
DOIs
StatePublished - Oct 18 2010

ASJC Scopus subject areas

  • Cell Biology

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    Malureanu, L., Jeganathan, K. B., Jin, F., Baker, D. J., Van Ree, J. H., Gullon, O., Chen, Z., Henley, J. R., & Van Deursen, J. M. (2010). Cdc20 hypomorphic mice fail to counteract de novo synthesis of cyclin B1 in mitosis. Journal of Cell Biology, 191(2), 313-329. https://doi.org/10.1083/jcb.201003090