| Autor: |
Jing Zhou, An-Chi Tien, Alberta, John A., Ficarro, Scott B., Griveau, Amelie, Yu Sun, Deshpande, Janhavee S., Card, Joseph D., Morgan-Smith, Meghan, Michowski, Wojciech, Hashizume, Rintaro, James, C. David, Ligon, Keith L., Snider, William D., Sicinski, Peter, Marto, Jarrod A., Rowitch, David H., Stiles, Charles D. |
| Zdroj: |
Cell Reports; Mar2017, Vol. 18 Issue 13, p3167-3177, 11p |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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