| First Author | Penas C | Year | 2015 |
| Journal | Cell Rep | Volume | 11 |
| Issue | 2 | Pages | 249-60 |
| PubMed ID | 25843713 | Mgi Jnum | J:228160 |
| Mgi Id | MGI:5705448 | Doi | 10.1016/j.celrep.2015.03.016 |
| Citation | Penas C, et al. (2015) Casein kinase 1delta is an APC/C(Cdh1) substrate that regulates cerebellar granule cell neurogenesis. Cell Rep 11(2):249-60 |
| abstractText | Although casein kinase 1delta (CK1delta) is at the center of multiple signaling pathways, its role in the expansion of CNS progenitor cells is unknown. Using mouse cerebellar granule cell progenitors (GCPs) as a model for brain neurogenesis, we demonstrate that the loss of CK1delta or treatment of GCPs with a highly selective small molecule inhibits GCP expansion. In contrast, CK1delta overexpression increases GCP proliferation. Thus, CK1delta appears to regulate GCP neurogenesis. CK1delta is targeted for proteolysis via the anaphase-promoting complex/cyclosome (APC/C(Cdh1)) ubiquitin ligase, and conditional deletion of the APC/C(Cdh1) activator Cdh1 in cerebellar GCPs results in higher levels of CK1delta. APC/C(Cdh1) also downregulates CK1delta during cell-cycle exit. Therefore, we conclude that APC/C(Cdh1) controls CK1delta levels to balance proliferation and cell-cycle exit in the developing CNS. Similar studies in medulloblastoma cells showed that CK1delta holds promise as a therapeutic target. |
