title: The APC/C and CBP/p300 cooperate to regulate transcription and cell-cycle progression.
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. 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. 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.
authors.affiliation: Cancer Research UK Institute for Cancer Studies, The Medical School, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. A.S.Turnell@bham.ac.uk
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Turnell
authors.forename: Grant S
authors.initials: GS
authors.lastname: Stewart
authors.forename: Roger J A
authors.initials: RJ
authors.lastname: Grand
authors.forename: Susan M
authors.initials: SM
authors.lastname: Rookes
authors.forename: Ashley
authors.initials: A
authors.lastname: Martin
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamano
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Elledge
authors.forename: Phillip H
authors.initials: PH
authors.lastname: Gallimore
mesh_terms: D017500:Adenovirus E1A Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D064193:Apc5 Subunit, Anaphase-Promoting Complex-Cyclosome; D064195:Apc7 Subunit, Anaphase-Promoting Complex-Cyclosome; D050882:CREB-Binding Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D017124:Conserved Sequence; D005786:Gene Expression Regulation; D006801:Humans; D008938:Mitosis; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014158:Transcription, Genetic; D043743:Ubiquitin-Protein Ligase Complexes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: C577375:ANAPC5 protein, human; C577399:ANAPC7 protein, human; D017500:Adenovirus E1A Proteins; D064193:Apc5 Subunit, Anaphase-Promoting Complex-Cyclosome; D064195:Apc7 Subunit, Anaphase-Promoting Complex-Cyclosome; D050882:CREB-Binding Protein; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome