Document Detail


Pediatric glioma-associated KIAA1549:BRAF expression regulates neuroglial cell growth in a cell type-specific and mTOR-dependent manner.
MedLine Citation:
PMID:  23152448     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-11-14
Journal Detail:
Title:  Genes & development     Volume:  26     ISSN:  1549-5477     ISO Abbreviation:  Genes Dev.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-04     Completed Date:  2013-01-25     Revised Date:  2014-04-08    
Medline Journal Info:
Nlm Unique ID:  8711660     Medline TA:  Genes Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2561-6     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
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
Ribosomal Protein S6 Kinases, 70-kDa / genetics
TOR Serine-Threonine Kinases / metabolism*
Tumor Suppressor Proteins / metabolism
Grant Support
ID/Acronym/Agency:
NS065547/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Neuropeptides; 0/Rheb protein, mouse; 0/Tumor Suppressor Proteins; 4JG2LF96VF/tuberous sclerosis complex 2 protein; EC 2.7.1.1/TOR Serine-Threonine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins B-raf; EC 2.7.11.1/Ribosomal Protein S6 Kinases, 70-kDa; EC 2.7.11.1/ribosomal protein S6 kinase, 70kD, polypeptide 1; EC 3.6.5.2/Monomeric GTP-Binding Proteins
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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