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

Authors
  • Kaul, Aparna
  • Chen, Yi-Hsien
  • Emnett, Ryan J
  • Dahiya, Sonika
  • Gutmann, David H
Type
Published Article
Journal
Genes & Development
Publisher
Cold Spring Harbor Laboratory
Publication Date
Dec 01, 2012
Volume
26
Issue
23
Pages
2561–2566
Identifiers
DOI: 10.1101/gad.200907.112
PMID: 23152448
Source
Medline
License
Unknown

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.

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