Pediatric glioma-associated KIAA1549:BRAF expression regulates neuroglial cell growth in a cell type-specific and mTOR-dependent manner.

Abstract	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.
Authors	Aparna Kaul, Yi-Hsien Chen, Ryan J Emnett, Sonika Dahiya, David H Gutmann
Journal	Genes & development (Genes Dev) Vol. 26 Issue 23 Pg. 2561-6 (Dec 01 2012) ISSN: 1549-5477 [Electronic] United States
PMID	23152448 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Neuropeptides Ras Homolog Enriched in Brain Protein Rheb protein, mouse TSC2 protein, human Tuberous Sclerosis Complex 2 Protein Tumor Suppressor Proteins Proto-Oncogene Proteins B-raf Ribosomal Protein S6 Kinases, 70-kDa TOR Serine-Threonine Kinases ribosomal protein S6 kinase, 70kD, polypeptide 1 Monomeric GTP-Binding Proteins
Topics	Animals Astrocytoma (pathology, physiopathology) Cell Proliferation Cells, Cultured Child Gene Expression Regulation, Neoplastic Glioma (pathology, physiopathology) Humans Mice Mice, Inbred C57BL Monomeric GTP-Binding Proteins (metabolism) Neuroglia (cytology, metabolism) Neuropeptides (metabolism) Phosphorylation Proto-Oncogene Proteins B-raf (genetics, metabolism) Ras Homolog Enriched in Brain Protein Ribosomal Protein S6 Kinases, 70-kDa (genetics) TOR Serine-Threonine Kinases (metabolism) Tuberous Sclerosis Complex 2 Protein Tumor Suppressor Proteins (metabolism)

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