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J Cell Biol. 2014 Oct 13;207(1):23-39. doi: 10.1083/jcb.201402041. Epub 2014 Oct 6.

Multiple mechanisms determine the order of APC/C substrate degradation in mitosis.

Author information

1
Department of Physiology and Department of Biochemistry and Biophysics and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158.
2
Center for Quantitative Biology and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China david.morgan@ucsf.edu tangc@pku.edu.cn.
3
Department of Physiology and Department of Biochemistry and Biophysics and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158 david.morgan@ucsf.edu tangc@pku.edu.cn.

Abstract

The ubiquitin protein ligase anaphase-promoting complex or cyclosome (APC/C) controls mitosis by promoting ordered degradation of securin, cyclins, and other proteins. The mechanisms underlying the timing of APC/C substrate degradation are poorly understood. We explored these mechanisms using quantitative fluorescence microscopy of GFP-tagged APC/C(Cdc20) substrates in living budding yeast cells. Degradation of the S cyclin, Clb5, begins early in mitosis, followed 6 min later by the degradation of securin and Dbf4. Anaphase begins when less than half of securin is degraded. The spindle assembly checkpoint delays the onset of Clb5 degradation but does not influence securin degradation. Early Clb5 degradation depends on its interaction with the Cdk1-Cks1 complex and the presence of a Cdc20-binding "ABBA motif" in its N-terminal region. The degradation of securin and Dbf4 is delayed by Cdk1-dependent phosphorylation near their Cdc20-binding sites. Thus, a remarkably diverse array of mechanisms generates robust ordering of APC/C(Cdc20) substrate destruction.

PMID:
25287299
PMCID:
PMC4195823
DOI:
10.1083/jcb.201402041
[Indexed for MEDLINE]
Free PMC Article

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