1. Cancer Research UK Institute for Cancer Studies, The Medical School, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
2. Verna & Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
3. Marie Curie Research Institute, The Chart, Oxted, Surrey RH8 OTL, UK
4. Department of Genetics, Center for Genetics and Genomics, and Howard Hughes Medical Institute, Harvard University Medical School, Boston, Massachusetts 02115, USA

Correspondence to: Andrew S. Turnell¹ Correspondence and requests for materials should be addressed to A.S.T. (Email: A.S.Turnell@bham.ac.uk).

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 cycle^{1, 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 E1A^{5, 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.

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.