PMID- 20670887
OWN - NLM
STAT- MEDLINE
DCOM- 20100820
LR  - 20220409
IS  - 1097-4164 (Electronic)
IS  - 1097-2765 (Print)
IS  - 1097-2765 (Linking)
VI  - 39
IP  - 2
DP  - 2010 Jul 30
TI  - Activation of a metabolic gene regulatory network downstream of mTOR complex 1.
PG  - 171-83
LID - 10.1016/j.molcel.2010.06.022 [doi]
AB  - Aberrant activation of the mammalian target of rapamycin complex 1 (mTORC1) is a 
      common molecular event in a variety of pathological settings, including genetic 
      tumor syndromes, cancer, and obesity. However, the cell-intrinsic consequences of 
      mTORC1 activation remain poorly defined. Through a combination of unbiased 
      genomic, metabolomic, and bioinformatic approaches, we demonstrate that mTORC1 
      activation is sufficient to stimulate specific metabolic pathways, including 
      glycolysis, the oxidative arm of the pentose phosphate pathway, and de novo lipid 
      biosynthesis. This is achieved through the activation of a transcriptional 
      program affecting metabolic gene targets of hypoxia-inducible factor (HIF1alpha) 
      and sterol regulatory element-binding protein (SREBP1 and SREBP2). We find that 
      SREBP1 and 2 promote proliferation downstream of mTORC1, and the activation of 
      these transcription factors is mediated by S6K1. Therefore, in addition to 
      promoting protein synthesis, mTORC1 activates specific bioenergetic and anabolic 
      cellular processes that are likely to contribute to human physiology and disease.
CI  - Copyright 2010 Elsevier Inc. All rights reserved.
FAU - Duvel, Katrin
AU  - Duvel K
AD  - Department of Genetics and Complex Diseases, Harvard School of Public Health, 
      Boston, MA 02115, USA.
FAU - Yecies, Jessica L
AU  - Yecies JL
FAU - Menon, Suchithra
AU  - Menon S
FAU - Raman, Pichai
AU  - Raman P
FAU - Lipovsky, Alex I
AU  - Lipovsky AI
FAU - Souza, Amanda L
AU  - Souza AL
FAU - Triantafellow, Ellen
AU  - Triantafellow E
FAU - Ma, Qicheng
AU  - Ma Q
FAU - Gorski, Regina
AU  - Gorski R
FAU - Cleaver, Stephen
AU  - Cleaver S
FAU - Vander Heiden, Matthew G
AU  - Vander Heiden MG
FAU - MacKeigan, Jeffrey P
AU  - MacKeigan JP
FAU - Finan, Peter M
AU  - Finan PM
FAU - Clish, Clary B
AU  - Clish CB
FAU - Murphy, Leon O
AU  - Murphy LO
FAU - Manning, Brendan D
AU  - Manning BD
LA  - eng
SI  - GEO/GSE21755
GR  - R01 CA122617-04/CA/NCI NIH HHS/United States
GR  - T90-DK070078/DK/NIDDK NIH HHS/United States
GR  - T90 DK070078/DK/NIDDK NIH HHS/United States
GR  - P01 CA120964/CA/NCI NIH HHS/United States
GR  - P01 CA120964-03/CA/NCI NIH HHS/United States
GR  - R01 CA122617/CA/NCI NIH HHS/United States
GR  - P01-CA120964/CA/NCI NIH HHS/United States
GR  - R01-CA122617/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Cell
JT  - Molecular cell
JID - 9802571
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Lipids)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Proteins)
RN  - 0 (Srebf1 protein, mouse)
RN  - 0 (Srebf2 protein, mouse)
RN  - 0 (Sterol Regulatory Element Binding Protein 1)
RN  - 0 (Sterol Regulatory Element Binding Protein 2)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 90-kDa)
RN  - EC 2.7.11.1 (Rps6ka1 protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Cell Line, Transformed
MH  - Cell Proliferation
MH  - Gene Expression Regulation/*physiology
MH  - Genomics/methods
MH  - Glycolysis/*physiology
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism
MH  - Lipids/*biosynthesis/genetics
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Metabolomics/methods
MH  - Mice
MH  - Multiprotein Complexes
MH  - Neoplasms/genetics/metabolism
MH  - Obesity/genetics/metabolism
MH  - Pentose Phosphate Pathway/*physiology
MH  - Protein Biosynthesis/*physiology
MH  - Proteins
MH  - Ribosomal Protein S6 Kinases, 90-kDa/genetics/metabolism
MH  - Sterol Regulatory Element Binding Protein 1/genetics/metabolism
MH  - Sterol Regulatory Element Binding Protein 2/genetics/metabolism
MH  - TOR Serine-Threonine Kinases
MH  - Transcription Factors/genetics/*metabolism
MH  - Transcription, Genetic/*physiology
PMC - PMC2946786
MID - NIHMS215770
EDAT- 2010/07/31 06:00
MHDA- 2010/08/21 06:00
PMCR- 2011/07/30
CRDT- 2010/07/31 06:00
PHST- 2010/01/18 00:00 [received]
PHST- 2010/04/07 00:00 [revised]
PHST- 2010/05/14 00:00 [accepted]
PHST- 2010/07/31 06:00 [entrez]
PHST- 2010/07/31 06:00 [pubmed]
PHST- 2010/08/21 06:00 [medline]
PHST- 2011/07/30 00:00 [pmc-release]
AID - S1097-2765(10)00463-6 [pii]
AID - 10.1016/j.molcel.2010.06.022 [doi]
PST - ppublish
SO  - Mol Cell. 2010 Jul 30;39(2):171-83. doi: 10.1016/j.molcel.2010.06.022.