@article{c9d14c78fbce41c6870cda49a6fcaa42,
title = "Casein kinase 1δ is an APC/CCdh1 substrate that regulates cerebellar granule cell neurogenesis",
abstract = "Although casein kinase 1δ (CK1δ) 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 CK1δ or treatment of GCPs with a highly selective small molecule inhibits GCP expansion. In contrast, CK1δ overexpression increases GCP proliferation. Thus, CK1δ appears to regulate GCP neurogenesis. CK1δ is targeted for proteolysis via the anaphasepromoting complex/cyclosome (APC/CCdh1) ubiquitin ligase, and conditional deletion of the APC/ CCdh1 activator Cdh1 in cerebellar GCPs results in higher levels of CK1δ. APC/CCdh1 also downregulates CK1δ during cell-cycle exit. Therefore, we conclude that APC/CCdh1 controls CK1δ levels to balance proliferation and cell-cycle exit in the developing CNS. Similar studies in medulloblastoma cells showed that CK1δ holds promise as a therapeutic target.",
author = "Clara Penas and Govek, {Eve Ellen} and Yin Fang and Vimal Ramachandran and Mark Daniel and Weiping Wang and Maloof, {Marie E.} and Rahaim, {Ronald J.} and Mathieu Bibian and Daisuke Kawauchi and David Finkelstein and Han, {Jeng Liang} and Jun Long and Bin Li and Robbins, {David J.} and Marcos Malumbres and Roussel, {Martine F.} and Roush, {William R.} and Hatten, {Mary E.} and Ayad, {Nagi G.}",
note = "Funding Information: We thank Dr. David Rowitch (University of California, San Francisco) for providing the Atoh1-Cre deleter line and Dr. Marc Kirschner for helpful discussions and critical reading of the manuscript. We also thank all members of the Center for Therapeutic Innovation (University of Miami) and the Department of Cancer Biology (Scripps Florida) for helpful suggestions. We thank Dr. Angela MacArthur and the Department of Scientific Editing at St. Jude Children{\textquoteright}s Research Hospital for helpful suggestions. This work was supported by R21 NS056991 (N.G.A.), R01NS067289 (N.G.A. and M.E.H.), NIH grant NCI CA-096832 (M.F.R.), NIH Molecular Library Screening Center Network grant U54MH074404 (W.R.R., Hugh Rosen, PI), Core Grant CA-021765 (M.F.R., D.K., and D.F.), the Anderson Fellowship (D.K.), and the American Lebanese-Syrian Associated Charities (ALSAC) of St. Jude Children's Research Hospital (M.F.R., D.K., and D.F.) as well as the Spanish Ministerio de Econom{\'i}a y Competitividad (MINECO, SAF2012-38215), Fundaci{\'o}n Ram{\'o}n Areces, Comunidad de Madrid (S2010/BMD-2470), and the European Union Seventh Framework Programme (MitoSys project; HEALTH-F5-2010-241548) (M.M.). ",
year = "2015",
doi = "10.1016/j.celrep.2015.03.016",
language = "English (US)",
volume = "11",
pages = "249--260",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "2",
}