- EMDB-4465: Cryo-EM structure of the APC/C-Cdc20-Cdk2-cyclinA2-Cks2 complex, ... -
ID or keywords:
Database: EMDB / ID: EMD-4465
Cryo-EM structure of the APC/C-Cdc20-Cdk2-cyclinA2-Cks2 complex, the D1 box class
Cryo-EM structure of the APC/C-Cdc20-Cdk2-cyclinA2-Cks2 complex, the D1 box class
(Cell division cycle protein ...Cell cycle) x 4
(Anaphase-promoting complex subunit ...) x 11
Function / homology
Function and homology information
APC/C:Cdc20 mediated degradation of mitotic proteins / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / Processing of DNA double-strand break ends / Autodegradation of Cdh1 by Cdh1:APC/C / Ub-specific processing proteases / SCF-beta-TrCP mediated degradation of Emi1 / APC/C:Cdc20 mediated degradation of Securin / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / RHO GTPases Activate Formins ...APC/C:Cdc20 mediated degradation of mitotic proteins / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / Processing of DNA double-strand break ends / Autodegradation of Cdh1 by Cdh1:APC/C / Ub-specific processing proteases / SCF-beta-TrCP mediated degradation of Emi1 / APC/C:Cdc20 mediated degradation of Securin / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / RHO GTPases Activate Formins / Regulation of TP53 Activity through Phosphorylation / Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase / Regulation of APC/C activators between G1/S and early anaphase / Phosphorylation of the APC/C / Phosphorylation of Emi1 / APC-Cdc20 mediated degradation of Nek2A / SCF(Skp2)-mediated degradation of p27/p21 / DNA Damage/Telomere Stress Induced Senescence / Separation of Sister Chromatids / Resolution of Sister Chromatid Cohesion / APC/C:Cdc20 mediated degradation of Cyclin B / Regulation of TP53 Degradation / Mitotic Prometaphase / Antigen processing: Ubiquitination & Proteasome degradation / Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 / Cyclin A:Cdk2-associated events at S phase entry / Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components / p53-Dependent G1 DNA Damage Response / Cyclin A/B1/B2 associated events during G2/M transition / CDK-mediated phosphorylation and removal of Cdc6 / Orc1 removal from chromatin / G2 Phase / Inactivation of APC/C via direct inhibition of the APC/C complex / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / G0 and Early G1 / Phosphorylation of proteins involved in the G2/M transition by Cyclin A:Cdc2 complexes / Senescence-Associated Secretory Phenotype (SASP) / regulation of mitotic cell cycle spindle assembly checkpoint / metaphase/anaphase transition of mitotic cell cycle / regulation of meiotic nuclear division / positive regulation of synapse maturation / ubiquitin-protein transferase activator activity / positive regulation of synaptic plasticity / positive regulation of mitotic metaphase/anaphase transition / anaphase-promoting complex / cullin-RING ubiquitin ligase complex / cellular response to luteinizing hormone stimulus / cellular response to cocaine / anaphase-promoting complex binding / regulation of exit from mitosis / regulation of mitotic metaphase/anaphase transition / cell cycle G1/S phase transition / ubiquitin-ubiquitin ligase activity / positive regulation of ubiquitin protein ligase activity / regulation of dendrite development / mitotic cell cycle phase transition / mitotic sister chromatid cohesion / male pronucleus / protein K11-linked ubiquitination / female pronucleus / cellular response to insulin-like growth factor stimulus / mitotic metaphase plate congression / cellular response to leptin stimulus / response to glucagon / cullin family protein binding / positive regulation of dendrite morphogenesis / cyclin-dependent protein serine/threonine kinase regulator activity / cochlea development / regulation of mitotic cell cycle / cellular response to platelet-derived growth factor stimulus / intracellular / positive regulation of axon extension / condensed chromosome kinetochore / mitotic spindle assembly checkpoint / regulation of DNA replication / mitotic spindle assembly / regulation of cyclin-dependent protein serine/threonine kinase activity / cyclin A2-CDK2 complex / histone phosphorylation / regulation of mitotic cell cycle phase transition / nuclear periphery / cyclin-dependent protein kinase holoenzyme complex / cellular response to nitric oxide / kinetochore / cellular response to estradiol stimulus / animal organ regeneration / spindle / ubiquitin protein ligase activity / spindle pole / positive regulation of fibroblast proliferation / ubiquitin-protein transferase activity / histone deacetylase binding / cellular response to hypoxia / anaphase-promoting complex-dependent catabolic process / mitotic cell cycle / Ras protein signal transduction / G2/M transition of mitotic cell cycle / ubiquitin-dependent protein catabolic process / protein phosphatase binding / protein C-terminus binding
Journal: Nat Commun / Year: 2019 Title: Cyclin A2 degradation during the spindle assembly checkpoint requires multiple binding modes to the APC/C. Authors: Suyang Zhang / Thomas Tischer / David Barford / Abstract: 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.
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