title: Insights into the anaphase-promoting complex: a molecular machine that regulates mitosis.
abstract: The anaphase-promoting complex/cyclosome (APC/C) is a large multimeric complex that functions as a RING domain E3 ubiquitin ligase to regulate ordered transitions through the cell cycle. It does so by controlling the ubiquitin-mediated proteolysis of cell cycle proteins, notably cyclins and securins, whose degradation triggers sister chromatid disjunction and mitotic exit. Regulation of APC/C activity and modulation of its substrate specificity are subject to intricate cell cycle checkpoints and control mechanisms involving the switching of substrate-specifying cofactors, association of regulatory protein complexes and post-translational modifications. This review discusses the recent progress towards understanding the overall architecture of the APC/C, the molecular basis for degron recognition and ubiquitin chain synthesis, and how these activities are regulated.
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors.forename: Leifu
authors.initials: L
authors.lastname: Chang
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. Electronic address: dbarford@mrc-lmb.cam.ac.uk.
authors.forename: David
authors.initials: D
authors.lastname: Barford
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D044783:F-Box Proteins / Q000378:metabolism; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints; D008938:Mitosis; D046912:Multiprotein Complexes / Q000378:metabolism*; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D059748:Proteolysis; D013379:Substrate Specificity; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D018797:Cell Cycle Proteins; D044783:F-Box Proteins; C498960:FBXO5 protein, human; D046912:Multiprotein Complexes; D025801:Ubiquitin; D064173:Anaphase-Promoting Complex-Cyclosome; D044767:Ubiquitin-Protein Ligases