title: Building a Regulatory Network with Short Linear Sequence Motifs: Lessons from the Degrons of the Anaphase-Promoting Complex.
abstract: The anaphase-promoting complex or cyclosome (APC/C) is a ubiquitin ligase that polyubiquitinates specific substrates at precise times in the cell cycle, thereby triggering the events of late mitosis in a strict order. The robust substrate specificity of the APC/C prevents the potentially deleterious degradation of non-APC/C substrates and also averts the cell-cycle errors and genomic instability that could result from mistimed degradation of APC/C targets. The APC/C recognizes short linear sequence motifs, or degrons, on its substrates. The specific and timely modification and degradation of APC/C substrates is likely to be modulated by variations in degron sequence and context. We discuss the extensive affinity, specificity, and selectivity determinants encoded in APC/C degrons, and we describe some of the extrinsic mechanisms that control APC/C-substrate recognition. As an archetype for protein motif-driven regulation of cell function, the APC/C-substrate interaction provides insights into the general properties of post-translational regulatory systems.
authors.affiliation: Conway Institute of Biomolecular and Biomedical Sciences, University College Dublin, Dublin 4, Ireland. Electronic address: norman.davey@ucd.ie.
authors.forename: Norman E
authors.initials: NE
authors.lastname: Davey
authors.affiliation: Departments of Physiology and Biochemistry & Biophysics, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: david.morgan@ucsf.edu.
authors.forename: David O
authors.initials: DO
authors.lastname: Morgan
mesh_terms: D020816:Amino Acid Motifs; D000705:Anaphase; D064173:Anaphase-Promoting Complex-Cyclosome / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D064199:Cdc20 Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D054730:Protein Interaction Domains and Motifs; D011499:Protein Processing, Post-Translational; D059748:Proteolysis; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D054875:Ubiquitination
chemical_list: D064199:Cdc20 Proteins; C577488:CDC20 protein, human; D064173:Anaphase-Promoting Complex-Cyclosome