title: Ubiquitin Ligases: Structure, Function, and Regulation.
abstract: Ubiquitin E3 ligases control every aspect of eukaryotic biology by promoting protein ubiquitination and degradation. At the end of a three-enzyme cascade, ubiquitin ligases mediate the transfer of ubiquitin from an E2 ubiquitin-conjugating enzyme to specific substrate proteins. Early investigations of E3s of the RING (really interesting new gene) and HECT (homologous to the E6AP carboxyl terminus) types shed light on their enzymatic activities, general architectures, and substrate degron-binding modes. Recent studies have provided deeper mechanistic insights into their catalysis, activation, and regulation. In this review, we summarize the current progress in structure-function studies of ubiquitin ligases as well as exciting new discoveries of novel classes of E3s and diverse substrate recognition mechanisms. Our increased understanding of ubiquitin ligase function and regulation has provided the rationale for developing E3-targeting therapeutics for the treatment of human diseases.
authors.affiliation: Howard Hughes Medical Institute and Department of Pharmacology, University of Washington, Seattle, Washington 98195; email: nzheng@uw.edu , nshabek@uw.edu.
authors.forename: Ning
authors.initials: N
authors.lastname: Zheng
authors.affiliation: Howard Hughes Medical Institute and Department of Pharmacology, University of Washington, Seattle, Washington 98195; email: nzheng@uw.edu , nshabek@uw.edu.
authors.forename: Nitzan
authors.initials: N
authors.lastname: Shabek
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015507:Drugs, Investigational / Q000138:chemical synthesis; D005057:Eukaryotic Cells / Q000378:metabolism* / Q000382:microbiology / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D008958:Models, Molecular; D010766:Phosphorylation; D054730:Protein Interaction Domains and Motifs; D011499:Protein Processing, Post-Translational; D059748:Proteolysis; D013379:Substrate Specificity; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D015507:Drugs, Investigational; D025801:Ubiquitin; D014764:Viral Proteins; D044767:Ubiquitin-Protein Ligases
keywords: PTM; agonist; degron; posttranslational modification; ubiquitin ligase; ubiquitination