| Autor: |
Jing Zhou, An-Chi Tien, John A. Alberta, Scott B. Ficarro, Amelie Griveau, Yu Sun, Janhavee S. Deshpande, Joseph D. Card, Meghan Morgan-Smith, Wojciech Michowski, Rintaro Hashizume, C. David James, Keith L. Ligon, William D. Snider, Peter Sicinski, Jarrod A. Marto, David H. Rowitch, Charles D. Stiles |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 18, Iss 13, Pp 3167-3177 (2017) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2017.03.003 |
| Popis: |
During development of the vertebrate CNS, the basic helix-loop-helix (bHLH) transcription factor Olig2 sustains replication competence of progenitor cells that give rise to neurons and oligodendrocytes. A pathological counterpart of this developmental function is seen in human glioma, wherein Olig2 is required for maintenance of stem-like cells that drive tumor growth. The mitogenic/gliomagenic functions of Olig2 are regulated by phosphorylation of a triple serine motif (S10, S13, and S14) in the amino terminus. Here, we identify a set of three serine/threonine protein kinases (glycogen synthase kinase 3α/β [GSK3α/β], casein kinase 2 [CK2], and cyclin-dependent kinases 1/2 [CDK1/2]) that are, collectively, both necessary and sufficient to phosphorylate the triple serine motif. We show that phosphorylation of the motif itself serves as a template to prime phosphorylation of additional serines and creates a highly charged “acid blob” in the amino terminus of Olig2. Finally, we show that small molecule inhibitors of this forward-feeding phosphorylation cascade have potential as glioma therapeutics. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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