Insights into the anaphase-promoting complex: a molecular machine that regulates mitosis

• Published in: Current opinion in structural biology Vol. 29; pp. 1 - 9
• Main Authors: Chang, Leifu, Barford, David
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2014
• Subjects: Anaphase-Promoting Complex-Cyclosome - metabolism; Cell Cycle Proteins - metabolism; F-Box Proteins - metabolism; Humans; M Phase Cell Cycle Checkpoints; Mitosis; Multiprotein Complexes - metabolism; Protein Conformation; Protein Processing, Post-Translational; Proteolysis; Substrate Specificity; Ubiquitin - metabolism; Ubiquitin-Protein Ligases - metabolism; Ubiquitination
• ISSN: 0959-440X; 1879-033X; 1879-033X
• DOI: 10.1016/j.sbi.2014.08.003

•Assignment of the complete secondary structure and subunit identification of the APC/C.•Mechanism of D box and KEN box recognition by APC/C-coactivator complexes.•Mechanism of stimulation of APC/C E3 ligase reaction by coactivator.•Principles of APC/C inhibition by regulators through blocking degron recognition and inhibiting ubiquitination reactions. 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.