metaphase/anaphase transition of cell cycle / metaphase/anaphase transition of meiosis I / Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components / mitotic checkpoint complex / positive regulation of anaphase-promoting complex-dependent catabolic process / regulation of meiotic nuclear division / Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase / regulation of mitotic cell cycle spindle assembly checkpoint / positive regulation of synapse maturation / Inactivation of APC/C via direct inhibition of the APC/C complex ...metaphase/anaphase transition of cell cycle / metaphase/anaphase transition of meiosis I / Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components / mitotic checkpoint complex / positive regulation of anaphase-promoting complex-dependent catabolic process / regulation of meiotic nuclear division / Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase / regulation of mitotic cell cycle spindle assembly checkpoint / positive regulation of synapse maturation / Inactivation of APC/C via direct inhibition of the APC/C complex / APC/C:Cdc20 mediated degradation of mitotic proteins / Phosphorylation of proteins involved in the G2/M transition by Cyclin A:Cdc2 complexes / Phosphorylation of Emi1 / cyclin A2-CDK1 complex / anaphase-promoting complex / cell cycle G1/S phase transition / Aberrant regulation of mitotic exit in cancer due to RB1 defects / cellular response to luteinizing hormone stimulus / regulation of meiotic cell cycle / metaphase/anaphase transition of mitotic cell cycle / anaphase-promoting complex-dependent catabolic process / positive regulation of synaptic plasticity / regulation of exit from mitosis / anaphase-promoting complex binding / Phosphorylation of the APC/C / mitotic cell cycle phase transition / positive regulation of mitotic metaphase/anaphase transition / Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 / positive regulation of ubiquitin protein ligase activity / ubiquitin ligase activator activity / cellular response to leptin stimulus / protein K11-linked ubiquitination / male pronucleus / female pronucleus / enzyme-substrate adaptor activity / positive regulation of dendrite morphogenesis / response to glucagon / cellular response to cocaine / regulation of mitotic metaphase/anaphase transition / cyclin-dependent protein serine/threonine kinase regulator activity / ubiquitin-ubiquitin ligase activity / cellular response to insulin-like growth factor stimulus / mitotic sister chromatid cohesion / mitotic metaphase chromosome alignment / positive regulation of DNA biosynthetic process / cochlea development / cellular response to platelet-derived growth factor stimulus / mitotic spindle assembly checkpoint signaling / cyclin A2-CDK2 complex / G2 Phase / p53-Dependent G1 DNA Damage Response / regulation of DNA replication / cullin family protein binding / Regulation of APC/C activators between G1/S and early anaphase / G0 and Early G1 / Telomere Extension By Telomerase / Transcriptional Regulation by VENTX / ubiquitin-like ligase-substrate adaptor activity / mitotic spindle assembly / cellular response to nitric oxide / positive regulation of axon extension / animal organ regeneration / protein K48-linked ubiquitination / heterochromatin / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / Cyclin A/B1/B2 associated events during G2/M transition / cyclin-dependent protein kinase holoenzyme complex / Cyclin A:Cdk2-associated events at S phase entry / Mitotic Prometaphase / EML4 and NUDC in mitotic spindle formation / Resolution of Sister Chromatid Cohesion / regulation of mitotic cell cycle / APC/C:Cdc20 mediated degradation of Cyclin B / APC-Cdc20 mediated degradation of Nek2A / nuclear periphery / post-translational protein modification / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / SCF-beta-TrCP mediated degradation of Emi1 / cellular response to estradiol stimulus / Assembly of the pre-replicative complex / RHO GTPases Activate Formins / 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 / brain development / DNA Damage/Telomere Stress Induced Senescence / CDK-mediated phosphorylation and removal of Cdc6 / mitotic spindle / kinetochore / SCF(Skp2)-mediated degradation of p27/p21 / spindle pole / spindle / Orc1 removal from chromatin / G1/S transition of mitotic cell cycle / Separation of Sister Chromatids / ubiquitin-protein transferase activity / G2/M transition of mitotic cell cycle / microtubule cytoskeleton / ubiquitin protein ligase activity 類似検索 - 分子機能
ジャーナル: Nat Commun / 年: 2019 タイトル: Cyclin A2 degradation during the spindle assembly checkpoint requires multiple binding modes to the APC/C. 著者: Suyang Zhang / Thomas Tischer / David Barford / 要旨: The anaphase-promoting complex/cyclosome (APC/C) orchestrates cell cycle progression by controlling the temporal degradation of specific cell cycle regulators. Although cyclin A2 and cyclin B1 are ...The anaphase-promoting complex/cyclosome (APC/C) orchestrates cell cycle progression by controlling the temporal degradation of specific cell cycle regulators. Although cyclin A2 and cyclin B1 are both targeted for degradation by the APC/C, during the spindle assembly checkpoint (SAC), the mitotic checkpoint complex (MCC) represses APC/C's activity towards cyclin B1, but not cyclin A2. Through structural, biochemical and in vivo analysis, we identify a non-canonical D box (D2) that is critical for cyclin A2 ubiquitination in vitro and degradation in vivo. During the SAC, cyclin A2 is ubiquitinated by the repressed APC/C-MCC, mediated by the cooperative engagement of its KEN and D2 boxes, ABBA motif, and the cofactor Cks. Once the SAC is satisfied, cyclin A2 binds APC/C-Cdc20 through two mutually exclusive binding modes, resulting in differential ubiquitination efficiency. Our findings reveal that a single substrate can engage an E3 ligase through multiple binding modes, affecting its degradation timing and efficiency.