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Proc Natl Acad Sci U S A. 2009 Oct 27;106(43):18213-8. doi: 10.1073/pnas.0907887106. Epub 2009 Oct 12.

Identification of a physiological E2 module for the human anaphase-promoting complex.

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  • 1Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.

Abstract

Ubiquitination by the anaphase-promoting complex (APC/C) is essential for proliferation in all eukaryotes. The human APC/C promotes the degradation of mitotic regulators by assembling K11-linked ubiquitin chains, the formation of which is initiated by its E2 UbcH10. Here, we identify the conserved Ube2S as a K11-specific chain elongating E2 for human and Drosophila APC/C. Ube2S depends on the cell cycle-dependent association with the APC/C activators Cdc20 and Cdh1 for its activity. While depletion of Ube2S already inhibits APC/C in cells, the loss of the complete UbcH10/Ube2S-module leads to dramatic stabilization of APC/C substrates, severe spindle defects, and a strong mitotic delay. Ube2S and UbcH10 are tightly co-regulated in the cell cycle by APC/C-dependent degradation. We conclude that UbcH10 and Ube2S constitute a physiological E2-module for APC/C, the activity of which is required for spindle assembly and cell division.

PMID:
19822757
[PubMed - indexed for MEDLINE]
PMCID:
PMC2775311
Free PMC Article

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