PMID- 24438340
OWN - NLM
STAT- MEDLINE
DCOM- 20141106
LR  - 20211021
IS  - 1944-9917 (Electronic)
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 28
IP  - 3
DP  - 2014 Mar
TI  - Steroid receptor coactivator 1 is an integrator of glucose and NAD+/NADH 
      homeostasis.
PG  - 395-405
LID - 10.1210/me.2013-1404 [doi]
AB  - Steroid receptor coactivator 1 (SRC-1) drives diverse gene expression programs 
      necessary for the dynamic regulation of cancer metastasis, inflammation and 
      gluconeogenesis, pointing to its overlapping roles as an oncoprotein and 
      integrator of cell metabolic programs. Nutrient utilization has been intensely 
      studied with regard to cellular adaptation in both cancer and noncancerous cells. 
      Nonproliferating cells consume glucose through the citric acid cycle to generate 
      NADH to fuel ATP generation via mitochondrial oxidative phosphorylation. In 
      contrast, cancer cells undergo metabolic reprogramming to support rapid 
      proliferation. To generate lipids, nucleotides, and proteins necessary for cell 
      division, most tumors switch from oxidative phosphorylation to glycolysis, a 
      phenomenon known as the Warburg Effect. Because SRC-1 is a key coactivator 
      responsible for driving a hepatic gluconeogenic program under fasting conditions, 
      we asked whether SRC-1 responds to alterations in nutrient availability to allow 
      for adaptive metabolism. Here we show SRC-1 is stabilized by the 26S proteasome 
      in the absence of glucose. RNA profiling was used to examine the effects of SRC-1 
      perturbation on gene expression in the absence or presence of glucose, revealing 
      that SRC-1 affects the expression of complex I of the mitochondrial electron 
      transport chain, a set of enzymes responsible for the conversion of NADH to 
      NAD(+). NAD(+) and NADH were subsequently identified as metabolites that underlie 
      SRC-1's response to glucose deprivation. Knockdown of SRC-1 in glycolytic cancer 
      cells abrogated their ability to grow in the absence of glucose consistent with 
      SRC-1's role in promoting cellular adaptation to reduced glucose availability.
FAU - Motamed, Massoud
AU  - Motamed M
AD  - Department of Molecular and Cellular Biology, Baylor College of Medicine, 
      Houston, Texas 77030.
FAU - Rajapakshe, Kimal I
AU  - Rajapakshe KI
FAU - Hartig, Sean M
AU  - Hartig SM
FAU - Coarfa, Cristian
AU  - Coarfa C
FAU - Moses, Robb E
AU  - Moses RE
FAU - Lonard, David M
AU  - Lonard DM
FAU - O'Malley, Bert W
AU  - O'Malley BW
LA  - eng
GR  - HD07857/HD/NICHD NIH HHS/United States
GR  - P30-DK079638/DK/NIDDK NIH HHS/United States
GR  - P01 DK059820/DK/NIDDK NIH HHS/United States
GR  - R01 HD008188/HD/NICHD NIH HHS/United States
GR  - P30 CA125123/CA/NCI NIH HHS/United States
GR  - P30 DK079638/DK/NIDDK NIH HHS/United States
GR  - K01 DK096093/DK/NIDDK NIH HHS/United States
GR  - 1K01DK096093/DK/NIDDK NIH HHS/United States
GR  - HD08188/HD/NICHD NIH HHS/United States
GR  - R01 HD007857/HD/NICHD NIH HHS/United States
GR  - P30CA125123/CA/NCI NIH HHS/United States
GR  - DK59820/DK/NIDDK NIH HHS/United States
GR  - F32 HD008188/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140117
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0U46U6E8UK (NAD)
RN  - EC 2.3.1.48 (Nuclear Receptor Coactivator 1)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
RN  - EC 7.1.1.2 (Electron Transport Complex I)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Cell Line, Tumor
MH  - Cell Survival
MH  - Electron Transport Complex I/metabolism
MH  - Energy Metabolism
MH  - Gene Expression
MH  - Glucose/*metabolism
MH  - *Homeostasis
MH  - Humans
MH  - NAD/*metabolism
MH  - Nuclear Receptor Coactivator 1/*physiology
MH  - Proteasome Endopeptidase Complex/metabolism
MH  - Protein Stability
MH  - Proteolysis
PMC - PMC3938540
EDAT- 2014/01/21 06:00
MHDA- 2014/11/07 06:00
PMCR- 2015/03/01
CRDT- 2014/01/21 06:00
PHST- 2014/01/21 06:00 [entrez]
PHST- 2014/01/21 06:00 [pubmed]
PHST- 2014/11/07 06:00 [medline]
PHST- 2015/03/01 00:00 [pmc-release]
AID - ME-13-1404 [pii]
AID - 10.1210/me.2013-1404 [doi]
PST - ppublish
SO  - Mol Endocrinol. 2014 Mar;28(3):395-405. doi: 10.1210/me.2013-1404. Epub 2014 Jan 
      17.