UbcH10 has a rate-limiting role in G1 phase but might not act in the spindle checkpoint or as part of an autonomous oscillator.
Ubiquitin-dependent proteolysis mediated by the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase lies at the heart of the cell cycle. The APC/C targets mitotic cyclins for destruction in mitosis and G1 phase and is then inactivated at S phase, thereby generating the alternating states of high and low cyclin-Cdk activity required for the alternation of mitosis and DNA replication. Two key questions are how the APC/C is held in check by the spindle-assembly checkpoint to delay cells in mitosis in the presence of improperly attached chromosomes, and how the APC/C is inactivated once cells exit mitosis. The ubiquitin-conjugating protein UbcH10 has been proposed to be crucial in the answers to both questions. However, here we show that the behaviour of UbcH10 is inconsistent with both a crucial role in the spindle checkpoint and in inactivating the APC/C as part of an autonomous oscillator. Instead, we find that the rate-limiting role of UbcH10 is only at the end of G1 phase, just before DNA replication begins.
Wellcome Trust/Cancer Research UK Gurdon Institute and Department of Zoology, University of Cambridge, Cambridge CB2 1QN, UK.
Adam
A
Walker
Claire
C
Acquaviva
Takahiro
T
Matsusaka
Lars
L
Koop
Jonathon
J
Pines
D019925:Cyclin A / Q000378:metabolism; D016193:G1 Phase; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D008941:Spindle Apparatus / Q000201:enzymology*; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism*
D019925:Cyclin A; C105156:UBE2C protein, human; D044763:Ubiquitin-Conjugating Enzymes