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Title | APC7 mediates ubiquitin signaling in constitutive heterochromatin in the developing mammalian brain. |
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Journal, issue, pages | Mol Cell, Vol. 82, Issue 1, Page 90-105.e13, Year 2022 |
Publish date | Jan 6, 2022 |
Authors | 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 / |
PubMed Abstract | 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. |
External links | Mol Cell / PubMed:34942119 / PubMed Central |
Methods | EM (single particle) |
Resolution | 7.4 - 7.6 Å |
Structure data | EMDB-25026: EMDB-25027: |
Source |
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