negative regulation of mitotic spindle pole body separation / Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase / positive regulation of mitotic actomyosin contractile ring contraction / deactivation of mitotic spindle assembly checkpoint / positive regulation of anaphase-promoting complex-dependent catabolic process / positive regulation of exit from mitosis / 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 ...negative regulation of mitotic spindle pole body separation / Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase / positive regulation of mitotic actomyosin contractile ring contraction / deactivation of mitotic spindle assembly checkpoint / positive regulation of anaphase-promoting complex-dependent catabolic process / positive regulation of exit from mitosis / 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 / 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 / positive regulation of synaptic plasticity / Phosphorylation of the APC/C / anaphase-promoting complex binding / (E3-independent) E2 ubiquitin-conjugating enzyme / positive regulation of mitotic metaphase/anaphase transition / positive regulation of dendrite morphogenesis / ubiquitin ligase activator activity / positive regulation of ubiquitin protein ligase activity / protein K11-linked ubiquitination / positive regulation of ubiquitin-dependent protein catabolic process / regulation of mitotic metaphase/anaphase transition / exit from mitosis / ubiquitin-ubiquitin ligase activity / E2 ubiquitin-conjugating enzyme / ubiquitin conjugating enzyme activity / Regulation of APC/C activators between G1/S and early anaphase / ubiquitin-like protein ligase binding / cullin family protein binding / Antigen processing: Ubiquitination & Proteasome degradation / Transcriptional Regulation by VENTX / ubiquitin ligase complex / positive regulation of axon extension / protein K48-linked ubiquitination / APC/C:Cdc20 mediated degradation of Cyclin B / APC-Cdc20 mediated degradation of Nek2A / cyclin binding / regulation of mitotic cell cycle / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / 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 / kinetochore / CDK-mediated phosphorylation and removal of Cdc6 / spindle / protein polyubiquitination / positive regulation of protein catabolic process / ubiquitin-protein transferase activity / Separation of Sister Chromatids / ubiquitin protein ligase activity / Antigen processing: Ubiquitination & Proteasome degradation / nervous system development / mitotic cell cycle / Senescence-Associated Secretory Phenotype (SASP) / ubiquitin-dependent protein catabolic process / protein phosphatase binding / molecular adaptor activity / proteasome-mediated ubiquitin-dependent protein catabolic process / cell differentiation / protein ubiquitination / cell division / negative regulation of gene expression / ubiquitin protein ligase binding / nucleolus / zinc ion binding / nucleoplasm / ATP binding / nucleus / plasma membrane / cytosol / cytoplasm 類似検索 - 分子機能
National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health & Human Development (NIH/NICHD)
5K08HD099314-02
米国
引用
ジャーナル: Mol Cell / 年: 2022 タイトル: APC7 mediates ubiquitin signaling in constitutive heterochromatin in the developing mammalian brain. 著者: Cole J Ferguson / Olivia Urso / Tatyana Bodrug / Brandon M Gassaway / Edmond R Watson / Jesuraj R Prabu / Pablo Lara-Gonzalez / Raquel C Martinez-Chacin / Dennis Y Wu / Karlla W Brigatti / ...著者: Cole J Ferguson / Olivia Urso / Tatyana Bodrug / Brandon M Gassaway / Edmond R Watson / Jesuraj R Prabu / Pablo Lara-Gonzalez / Raquel C Martinez-Chacin / Dennis Y Wu / Karlla W Brigatti / Erik G Puffenberger / Cora M Taylor / Barbara Haas-Givler / Robert N Jinks / Kevin A Strauss / Arshad Desai / Harrison W Gabel / Steven P Gygi / Brenda A Schulman / Nicholas G Brown / Azad Bonni / 要旨: Neurodevelopmental cognitive disorders provide insights into mechanisms of human brain development. Here, we report an intellectual disability syndrome caused by the loss of APC7, a core component of ...Neurodevelopmental cognitive disorders provide insights into mechanisms of human brain development. Here, we report an intellectual disability syndrome caused by the loss of APC7, a core component of the E3 ubiquitin ligase anaphase promoting complex (APC). In mechanistic studies, we uncover a critical role for APC7 during the recruitment and ubiquitination of APC substrates. In proteomics analyses of the brain from mice harboring the patient-specific APC7 mutation, we identify the chromatin-associated protein Ki-67 as an APC7-dependent substrate of the APC in neurons. Conditional knockout of the APC coactivator protein Cdh1, but not Cdc20, leads to the accumulation of Ki-67 protein in neurons in vivo, suggesting that APC7 is required for the function of Cdh1-APC in the brain. Deregulated neuronal Ki-67 upon APC7 loss localizes predominantly to constitutive heterochromatin. Our findings define an essential function for APC7 and Cdh1-APC in neuronal heterochromatin regulation, with implications for understanding human brain development and disease.