PMID- 23152448
OWN - NLM
STAT- MEDLINE
DCOM- 20130125
LR  - 20240109
IS  - 1549-5477 (Electronic)
IS  - 0890-9369 (Print)
IS  - 0890-9369 (Linking)
VI  - 26
IP  - 23
DP  - 2012 Dec 1
TI  - Pediatric glioma-associated KIAA1549:BRAF expression regulates neuroglial cell 
      growth in a cell type-specific and mTOR-dependent manner.
PG  - 2561-6
LID - 10.1101/gad.200907.112 [doi]
AB  - 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.
FAU - Kaul, Aparna
AU  - Kaul A
AD  - Department of Neurology, Washington University School of Medicine, St. Louis, MO 
      63108, USA.
FAU - Chen, Yi-Hsien
AU  - Chen YH
FAU - Emnett, Ryan J
AU  - Emnett RJ
FAU - Dahiya, Sonika
AU  - Dahiya S
FAU - Gutmann, David H
AU  - Gutmann DH
LA  - eng
GR  - R01 NS065547/NS/NINDS NIH HHS/United States
GR  - NS065547/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20121114
PL  - United States
TA  - Genes Dev
JT  - Genes & development
JID - 8711660
RN  - 0 (Neuropeptides)
RN  - 0 (Ras Homolog Enriched in Brain Protein)
RN  - 0 (Rheb protein, mouse)
RN  - 0 (TSC2 protein, human)
RN  - 0 (Tuberous Sclerosis Complex 2 Protein)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (ribosomal protein S6 kinase, 70kD, polypeptide 1)
RN  - EC 3.6.5.2 (Monomeric GTP-Binding Proteins)
SB  - IM
MH  - Animals
MH  - Astrocytoma/pathology/physiopathology
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Child
MH  - *Gene Expression Regulation, Neoplastic
MH  - Glioma/*pathology/physiopathology
MH  - Humans
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Monomeric GTP-Binding Proteins/metabolism
MH  - Neuroglia/*cytology/metabolism
MH  - Neuropeptides/metabolism
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins B-raf/genetics/metabolism
MH  - Ras Homolog Enriched in Brain Protein
MH  - Ribosomal Protein S6 Kinases, 70-kDa/genetics
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Tuberous Sclerosis Complex 2 Protein
MH  - Tumor Suppressor Proteins/metabolism
PMC - PMC3521628
EDAT- 2012/11/16 06:00
MHDA- 2013/01/26 06:00
PMCR- 2013/06/01
CRDT- 2012/11/16 06:00
PHST- 2012/11/16 06:00 [entrez]
PHST- 2012/11/16 06:00 [pubmed]
PHST- 2013/01/26 06:00 [medline]
PHST- 2013/06/01 00:00 [pmc-release]
AID - gad.200907.112 [pii]
AID - 10.1101/gad.200907.112 [doi]
PST - ppublish
SO  - Genes Dev. 2012 Dec 1;26(23):2561-6. doi: 10.1101/gad.200907.112. Epub 2012 Nov 
      14.