negative regulation of diacylglycerol biosynthetic process / protein localization to septin ring / mitotic morphogenesis checkpoint signaling / cellular bud neck septin ring / positive regulation of anaphase-promoting complex-dependent catabolic process / protein K27-linked ubiquitination / regulation of meiotic nuclear division / protein K29-linked ubiquitination / free ubiquitin chain polymerization / positive regulation of synapse maturation ...negative regulation of diacylglycerol biosynthetic process / protein localization to septin ring / mitotic morphogenesis checkpoint signaling / cellular bud neck septin ring / positive regulation of anaphase-promoting complex-dependent catabolic process / protein K27-linked ubiquitination / regulation of meiotic nuclear division / protein K29-linked ubiquitination / free ubiquitin chain polymerization / positive regulation of synapse maturation / Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase / regulation of mitotic cell cycle spindle assembly checkpoint / Inactivation of APC/C via direct inhibition of the APC/C complex / APC/C:Cdc20 mediated degradation of mitotic proteins / positive regulation of synaptic plasticity / Phosphorylation of Emi1 / anaphase-promoting complex / Aberrant regulation of mitotic exit in cancer due to RB1 defects / protein branched polyubiquitination / metaphase/anaphase transition of mitotic cell cycle / regulation of meiotic cell cycle / anaphase-promoting complex-dependent catabolic process / lens fiber cell differentiation / Phosphorylation of the APC/C / regulation of exit from mitosis / anaphase-promoting complex binding / cellular bud neck / protein K6-linked ubiquitination / positive regulation of mitotic metaphase/anaphase transition / positive regulation of dendrite morphogenesis / positive regulation of ubiquitin protein ligase activity / ubiquitin ligase activator activity / exit from mitosis / protein K11-linked ubiquitination / symbiont entry into host cell via disruption of host cell glycocalyx / regulation of mitotic metaphase/anaphase transition / ubiquitin-ubiquitin ligase activity / E2 ubiquitin-conjugating enzyme / mitotic metaphase chromosome alignment / symbiont entry into host cell via disruption of host cell envelope / virus tail / mitotic G2 DNA damage checkpoint signaling / ubiquitin conjugating enzyme activity / Regulation of APC/C activators between G1/S and early anaphase / cullin family protein binding / Transcriptional Regulation by VENTX / negative regulation of cellular senescence / protein K63-linked ubiquitination / enzyme-substrate adaptor activity / ubiquitin-like ligase-substrate adaptor activity / APC/C:Cdc20 mediated degradation of Cyclin B / positive regulation of axon extension / protein K48-linked ubiquitination / APC-Cdc20 mediated degradation of Nek2A / heterochromatin / intercellular bridge / Cyclin A:Cdk2-associated events at S phase entry / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / nuclear periphery / SCF-beta-TrCP mediated degradation of Emi1 / regulation of mitotic cell cycle / Assembly of the pre-replicative complex / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / protein catabolic process / CDK-mediated phosphorylation and removal of Cdc6 / protein modification process / brain development / kinetochore / spindle / Separation of Sister Chromatids / protein polyubiquitination / neuron projection development / ubiquitin-protein transferase activity / G2/M transition of mitotic cell cycle / mitotic spindle / Antigen processing: Ubiquitination & Proteasome degradation / ubiquitin protein ligase activity / nervous system development / mitotic cell cycle / Senescence-Associated Secretory Phenotype (SASP) / microtubule cytoskeleton / ubiquitin-dependent protein catabolic process / protein phosphatase binding / molecular adaptor activity / nuclear membrane / proteasome-mediated ubiquitin-dependent protein catabolic process / cell differentiation / non-specific serine/threonine protein kinase / protein ubiquitination / protein kinase activity / regulation of cell cycle / negative regulation of gene expression / cell division / protein serine kinase activity / DNA repair / protein serine/threonine kinase activity / intracellular membrane-bounded organelle 類似検索 - 分子機能
ジャーナル: Cell / 年: 2016 タイトル: Dual RING E3 Architectures Regulate Multiubiquitination and Ubiquitin Chain Elongation by APC/C. 著者: Nicholas G Brown / Ryan VanderLinden / Edmond R Watson / Florian Weissmann / Alban Ordureau / Kuen-Phon Wu / Wei Zhang / Shanshan Yu / Peter Y Mercredi / Joseph S Harrison / Iain F Davidson / ...著者: Nicholas G Brown / Ryan VanderLinden / Edmond R Watson / Florian Weissmann / Alban Ordureau / Kuen-Phon Wu / Wei Zhang / Shanshan Yu / Peter Y Mercredi / Joseph S Harrison / Iain F Davidson / Renping Qiao / Ying Lu / Prakash Dube / Michael R Brunner / Christy R R Grace / Darcie J Miller / David Haselbach / Marc A Jarvis / Masaya Yamaguchi / David Yanishevski / Georg Petzold / Sachdev S Sidhu / Brian Kuhlman / Marc W Kirschner / J Wade Harper / Jan-Michael Peters / Holger Stark / Brenda A Schulman / 要旨: Protein ubiquitination involves E1, E2, and E3 trienzyme cascades. E2 and RING E3 enzymes often collaborate to first prime a substrate with a single ubiquitin (UB) and then achieve different forms of ...Protein ubiquitination involves E1, E2, and E3 trienzyme cascades. E2 and RING E3 enzymes often collaborate to first prime a substrate with a single ubiquitin (UB) and then achieve different forms of polyubiquitination: multiubiquitination of several sites and elongation of linkage-specific UB chains. Here, cryo-EM and biochemistry show that the human E3 anaphase-promoting complex/cyclosome (APC/C) and its two partner E2s, UBE2C (aka UBCH10) and UBE2S, adopt specialized catalytic architectures for these two distinct forms of polyubiquitination. The APC/C RING constrains UBE2C proximal to a substrate and simultaneously binds a substrate-linked UB to drive processive multiubiquitination. Alternatively, during UB chain elongation, the RING does not bind UBE2S but rather lures an evolving substrate-linked UB to UBE2S positioned through a cullin interaction to generate a Lys11-linked chain. Our findings define mechanisms of APC/C regulation, and establish principles by which specialized E3-E2-substrate-UB architectures control different forms of polyubiquitination.