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Volume 272, Number 4,
Issue of January 24, 1997
pp. 2163-2166
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
"Spot 14" Protein Functions at the Pretranslational Level in
the Regulation of Hepatic Metabolism by Thyroid Hormone and
Glucose
(Received for publication, August 27, 1996, and in revised form, October 24, 1996)
Suzanne B.
Brown
,
Marybeth
Maloney
and
William B.
Kinlaw
From the Department of Medicine, Division of Endocrinology and
Metabolism, Dartmouth Medical School,
Lebanon, New Hampshire 03756
"Spot 14" protein appears rapidly in nuclei
of hepatocytes exposed to glucose and thyroid hormone. Exposure of
glucose- and T3-treated hepatocytes to a spot 14 antisense
oligonucleotide inhibited induction of mRNAs encoding malic enzyme,
ATP citrate-lyase, fatty acid synthase, liver-type pyruvate kinase,
phosphoenolpyruvate carboxykinase, and type I deiodinase but not
hydroxymethylglutaryl-CoA reductase, cytochrome c, and
actin mRNAs. Induction of spot 14, ATP citrate-lyase, and fatty
acid synthase polypeptides, but not propionyl-CoA carboxylase and
mitochondrial pyruvate carboxylase, was inhibited. Antisense treatment
of hepatocytes transfected with a reporter controlled by a glucose- and
T3-inducible fragment of the pyruvate kinase gene promoter
inhibited reporter activity, as did cotransfection of the reporter and
a spot 14 antisense plasmid. Spot 14 protein acts in the induction of
mRNAs coding for key lipogenic (malic enzyme, ATP citrate-lyase,
fatty acid synthase), glycolytic (pyruvate kinase), and gluconeogenic
enzymes (phosphoenolpyruvate carboxykinase), as well as the
diet-responsive type I deiodinase, but not those involved in
mitochondrial respiration (cytochrome c) or cholesterol
synthesis (hydroxymethylglutaryl-CoA reductase). Transfection
experiments indicated that these effects are mediated at the
transcriptional level. The protein functions in the activation of genes
involved in metabolic switching between the fasted and fed states in
liver.

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Copyright © 1997 by the American Society for Biochemistry and Molecular Biology.
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