Identification of a physiological E2 module for the human anaphase-promoting complex.
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.
Williamson
Adam
A
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Wickliffe
Katherine E
KE
Mellone
Barbara G
BG
Song
Ling
L
Karpen
Gary H
GH
Rape
Michael
M
D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D055162:Biocatalysis; D004331:Drosophila melanogaster / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D011485:Protein Binding; D025801:Ubiquitin / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism*; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism*
D025801:Ubiquitin; C105156:UBE2C protein, human; C544962:Ube2S protein, human; D044763:Ubiquitin-Conjugating Enzymes; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome