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TitleAPC7 mediates ubiquitin signaling in constitutive heterochromatin in the developing mammalian brain.
Journal, issue, pagesMol Cell, Vol. 82, Issue 1, Page 90-105.e13, Year 2022
Publish dateJan 6, 2022
AuthorsCole 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 /
PubMed AbstractNeurodevelopmental 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.
External linksMol Cell / PubMed:34942119 / PubMed Central
MethodsEM (single particle)
Resolution7.4 - 7.6 Å
Structure data

EMDB-25026:
Anaphase Promoting Complex delta APC7
Method: EM (single particle) / Resolution: 7.4 Å

EMDB-25027:
Anaphase Promoting Complex delta APC7 + UBE2C,substrate,UbV,CDH1
Method: EM (single particle) / Resolution: 7.6 Å

Source
  • Homo sapiens (human)

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