| First Author | Zhou J | Year | 2017 |
| Journal | Cell Rep | Volume | 18 |
| Issue | 13 | Pages | 3167-3177 |
| PubMed ID | 28355568 | Mgi Jnum | J:250997 |
| Mgi Id | MGI:6103665 | Doi | 10.1016/j.celrep.2017.03.003 |
| Citation | Zhou J, et al. (2017) A Sequentially Priming Phosphorylation Cascade Activates the Gliomagenic Transcription Factor Olig2. Cell Rep 18(13):3167-3177 |
| abstractText | 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 3alpha/beta [GSK3alpha/beta], 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. |
