| First Author | Ferguson CJ | Year | 2022 |
| Journal | Mol Cell | Volume | 82 |
| Issue | 1 | Pages | 90-105.e13 |
| PubMed ID | 34942119 | Mgi Jnum | J:320745 |
| Mgi Id | MGI:6874704 | Doi | 10.1016/j.molcel.2021.11.031 |
| Citation | Ferguson CJ, et al. (2022) APC7 mediates ubiquitin signaling in constitutive heterochromatin in the developing mammalian brain. Mol Cell 82(1):90-105.e13 |
| abstractText | 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. |
