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(Received for publication, October 8, 1996)
From the We demonstrate that the mRNA levels of
glycerol-3-phosphate acyltransferase (GPAT), a mitochondrial enzyme
catalyzing the initial step in glycerolipid synthesis, are induced
during the differentiation of 3T3-L1 preadipocytes to adipocytes and
following ectopic expression of rat adipocyte determination and
differentiation factor 1 (ADD1), a protein with high homology to the
human sterol regulatory element-binding protein-1 (SREBP-1). The
increase in GPAT mRNA levels that occurs during differentiation is
partially prevented by ectopic expression of a dominant negative form
of ADD1.
Nucleotide sequences corresponding to the proximal promoter of the
murine mitochondrial GPAT gene (Jerkins, A. A., Liu, W. R., Lee, S.,
and Sul, H. S. (1995) J. Biol. Chem. 270, 1416-1421) bound SREBP-1a and NF-Y in electromobility shift assays. In addition, GPAT promoter-luciferase reporter genes were stimulated by
co-expression of SREBP-1a. This increase was attenuated when either a
dominant negative form of NF-Y was co-transfected into the cells or
when the GPAT promoter contained mutations in the putative binding sites for SREBP-1a or NF-Y. These studies demonstrate that the regulated expression of the mitochondrial GPAT gene requires both NF-Y
and ADD1/SREBPs. Thus, SREBPs/ADD1 regulate not only genes involved in
cholesterol homeostasis and fatty acid synthesis but also a key enzyme
in glycerolipid synthesis.
Volume 272, Number 11,
Issue of March 14, 1997
pp. 7298-7305
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
,
,
,
and
Departments of Biological Chemistry and
Medicine and the Molecular Biology Institute, UCLA, Los Angeles,
California 90095 and the 
Dana-Faber Cancer Institute and
Department of Cell Biology, Harvard Medical School,
Boston, Massachusetts 02115
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|
|
|
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|
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|
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|
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|
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|
|
|
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|
|
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|
|
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|
|
|
|
|
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I. Shimomura, H. Shimano, B. S. Korn, Y. Bashmakov, and J. D. Horton Nuclear Sterol Regulatory Element-binding Proteins Activate Genes Responsible for the Entire Program of Unsaturated Fatty Acid Biosynthesis in Transgenic Mouse Liver J. Biol. Chem., December 25, 1998; 273(52): 35299 - 35306. [Abstract] [Full Text] [PDF]
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M. Boizard, X. Le Liepvre, P. Lemarchand, F. Foufelle, P. Ferre, and I. Dugail Obesity-related Overexpression of Fatty-acid Synthase Gene in Adipose Tissue Involves Sterol Regulatory Element-binding Protein Transcription Factors J. Biol. Chem., October 30, 1998; 273(44): 29164 - 29171. [Abstract] [Full Text] [PDF]
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R. B. Rawson, D. Cheng, M. S. Brown, and J. L. Goldstein Isolation of Cholesterol-requiring Mutant Chinese Hamster Ovary Cells with Defects in Cleavage of Sterol Regulatory Element-binding Proteins at Site 1 J. Biol. Chem., October 23, 1998; 273(43): 28261 - 28269. [Abstract] [Full Text] [PDF]
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I. Shimomura, R. E. Hammer, J. A. Richardson, S. Ikemoto, Y. Bashmakov, J. L. Goldstein, and M. S. Brown Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-1c in adipose tissue: model for congenital generalized lipodystrophy Genes & Dev., October 15, 1998; 12(20): 3182 - 3194. [Abstract] [Full Text]
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J.-t. Pai, O. Guryev, M. S. Brown, and J. L. Goldstein Differential Stimulation of Cholesterol and Unsaturated Fatty Acid Biosynthesis in Cells Expressing Individual Nuclear Sterol Regulatory Element-binding Proteins J. Biol. Chem., October 2, 1998; 273(40): 26138 - 26148. [Abstract] [Full Text] [PDF]
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J. Ericsson, J. M. Greene, K. C. Carter, B. K. Shell, D. R. Duan, C. Florence, and P. A. Edwards Human geranylgeranyl diphosphate synthase: isolation of the cDNA, chromosomal mapping and tissue expression J. Lipid Res., September 1, 1998; 39(9): 1731 - 1739. [Abstract] [Full Text]
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R. A. Chouinard Jr., Y. Luo, T. F. Osborne, A. Walsh, and A. R. Tall Sterol Regulatory Element Binding Protein-1 Activates the Cholesteryl Ester Transfer Protein Gene in Vivo but Is Not Required for Sterol Up-regulation of Gene Expression J. Biol. Chem., August 28, 1998; 273(35): 22409 - 22414. [Abstract] [Full Text] [PDF]
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