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oai:repisalud.isciii.es:20.500.12105/102892024-11-29T19:08:07Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Penas, Clara author Govek, Eve-Ellen author Fang, Yin author Ramachandran, Vimal author Daniel, Mark author Wang, Weiping author Maloof, Marie E author Rahaim, Ronald J author Bibian, Mathieu author Kawauchi, Daisuke author Finkelstein, David author Han, Jeng-Liang author Long, Jun author Li, Bin author Robbins, David J author Roussel, Martine F author Roush, William R author Hatten, Mary E author Ayad, Nagi G author 2015-04-14 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 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 CK1δ. APC/C(Cdh1) also downregulates CK1δ during cell-cycle exit. Therefore, we conclude that APC/C(Cdh1) 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. Cell Rep . 2015 ;11(2):249-60. http://hdl.handle.net/20.500.12105/10289 25843713 10.1016/j.celrep.2015.03.016 2211-1247 Cell reports MITOTIC ENTRY UBIQUITINATION MEDULLOBLASTOMA D-BOX FAMILY MOUSE MODEL SONIC HEDGEHOG DEPENDENT DEGRADATION ANAPHASE PROMOTING COMPLEX Casein kinase 1δ is an APC/C(Cdh1) substrate that regulates cerebellar granule cell neurogenesis.