| First Author | Kaul A | Year | 2012 |
| Journal | Genes Dev | Volume | 26 |
| Issue | 23 | Pages | 2561-6 |
| PubMed ID | 23152448 | Mgi Jnum | J:191207 |
| Mgi Id | MGI:5461252 | Doi | 10.1101/gad.200907.112 |
| Citation | Kaul A, et al. (2012) Pediatric glioma-associated KIAA1549:BRAF expression regulates neuroglial cell growth in a cell type-specific and mTOR-dependent manner. Genes Dev 26(23):2561-6 |
| abstractText | Tandem duplications involving the BRAF kinase gene have recently been identified as the most frequent genetic alteration in sporadic pediatric glioma, creating a novel fusion protein (f-BRAF) with increased BRAF activity. To define the role of f-BRAF in gliomagenesis, we demonstrate that f-BRAF regulates neural stem cell (NSC), but not astrocyte, proliferation and is sufficient to induce glioma-like lesions in mice. Moreover, f-BRAF-driven NSC proliferation results from tuberin/Rheb-mediated mammalian target of rapamycin (mTOR) hyperactivation, leading to S6-kinase-dependent degradation of p27. Collectively, these results establish mTOR pathway activation as a key growth regulatory mechanism common to both sporadic and familial low-grade gliomas in children. |
