PMID- 17030509
OWN - NLM
STAT- MEDLINE
DCOM- 20070125
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 281
IP  - 49
DP  - 2006 Dec 8
TI  - Phosphatidylinositol 3-kinase-dependent modulation of carnitine 
      palmitoyltransferase 1A expression regulates lipid metabolism during 
      hematopoietic cell growth.
PG  - 37372-80
AB  - An abundant supply of extracellular nutrients is believed to be sufficient to 
      suppress catabolism of cellular macromolecules. Here we show that, despite 
      abundant extracellular nutrients, interleukin-3-deprived hematopoietic cells 
      begin to catabolize intracellular lipids. Constitutive Akt activation blunts the 
      increased beta-oxidation that accompanies growth factor withdrawal, and in growth 
      factor-replete cells, phosphatidylinositol 3-kinase (PI3K) signaling is required 
      to suppress lipid catabolism. Surprisingly, PI3K and Akt exert these effects by 
      suppressing expression of the beta-oxidation enzyme carnitine 
      palmitoyltransferase 1A (CPT1A). Cells expressing a short hairpin RNA against 
      CPT1A fail to induce beta-oxidation in response to growth factor withdrawal and 
      are unable to survive glucose deprivation. When CPT1A is constitutively 
      expressed, growth factor stimulation fails to repress beta-oxidation. As a 
      result, both net lipid synthesis and cell proliferation are diminished. Together, 
      these results demonstrate that modulation of CPT1A expression by PI3K-dependent 
      signaling is the major mechanism by which cells suppress beta-oxidation during 
      anabolic growth.
FAU - Deberardinis, Ralph J
AU  - Deberardinis RJ
AD  - Abramson Family Cancer Research Institute, Department of Cancer Biology, 
      University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, 
      USA.
FAU - Lum, Julian J
AU  - Lum JJ
FAU - Thompson, Craig B
AU  - Thompson CB
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20061009
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - EC 2.3.1.21 (Carnitine O-Palmitoyltransferase)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/*cytology/*metabolism
MH  - Carnitine O-Palmitoyltransferase/genetics/*metabolism
MH  - Cell Division
MH  - Cell Line
MH  - Female
MH  - Gene Expression
MH  - *Lipid Metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Oxidation-Reduction
MH  - Phosphatidylinositol 3-Kinases/*metabolism
EDAT- 2006/10/13 09:00
MHDA- 2007/01/26 09:00
CRDT- 2006/10/13 09:00
PHST- 2006/10/13 09:00 [pubmed]
PHST- 2007/01/26 09:00 [medline]
PHST- 2006/10/13 09:00 [entrez]
AID - S0021-9258(20)71911-3 [pii]
AID - 10.1074/jbc.M608372200 [doi]
PST - ppublish
SO  - J Biol Chem. 2006 Dec 8;281(49):37372-80. doi: 10.1074/jbc.M608372200. Epub 2006 
      Oct 9.