Author
Listed:
- Andrew S. Turnell
(The Medical School, The University of Birmingham)
- Grant S. Stewart
(The Medical School, The University of Birmingham
Baylor College of Medicine
Baylor College of Medicine)
- Roger J. A. Grand
(The Medical School, The University of Birmingham)
- Susan M. Rookes
(The Medical School, The University of Birmingham)
- Ashley Martin
(The Medical School, The University of Birmingham)
- Hiroyuki Yamano
(The Chart)
- Stephen J. Elledge
(Baylor College of Medicine
Baylor College of Medicine
Harvard University Medical School)
- Phillip H. Gallimore
(The Medical School, The University of Birmingham)
Abstract
The anaphase-promoting complex/cyclosome (APC/C) is a multicomponent E3 ubiquitin ligase that, by targeting protein substrates for 26S proteasome-mediated degradation through ubiquitination, coordinates the temporal progression of eukaryotic cells through mitosis and the subsequent G1 phase of the cell cycle1,2,3,4. Other functions of the APC/C are, however, less well defined. Here we show that two APC/C components, APC5 and APC7, interact directly with the coactivators CBP and p300 through protein–protein interaction domains that are evolutionarily conserved in adenovirus E1A5,6,7,8. This interaction stimulates intrinsic CBP/p300 acetyltransferase activity and potentiates CBP/p300-dependent transcription. We also show that APC5 and APC7 suppress E1A-mediated transformation in a CBP/p300-dependent manner, indicating that these components of the APC/C may be targeted during cellular transformation. Furthermore, we establish that CBP is required in APC/C function; specifically, gene ablation of CBP by RNA-mediated interference markedly reduces the E3 ubiquitin ligase activity of the APC/C and the progression of cells through mitosis. Taken together, our results define discrete roles for the APC/C–CBP/p300 complexes in growth regulation.
Suggested Citation
Andrew S. Turnell & Grant S. Stewart & Roger J. A. Grand & Susan M. Rookes & Ashley Martin & Hiroyuki Yamano & Stephen J. Elledge & Phillip H. Gallimore, 2005.
"The APC/C and CBP/p300 cooperate to regulate transcription and cell-cycle progression,"
Nature, Nature, vol. 438(7068), pages 690-695, December.
Handle:
RePEc:nat:nature:v:438:y:2005:i:7068:d:10.1038_nature04151
DOI: 10.1038/nature04151
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