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(Received for publication, February 11, 1997, and in revised form, March 31, 1997)
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From the In mammals, plasma concentrations of amino acids
are affected by nutritional or pathological conditions. Here we
examined the role of amino acid limitation in regulating the expression of CHOP, a CCAAT/enhancer binding protein (C/EBP)-related
gene. CHOP protein is capable of interacting with other C/EBPs to
modify their DNA binding activities and may function as a negative
regulator of these transcription factors. Our data show that leucine
limitation in human cell lines leads to induction of CHOP
mRNA and protein in a dose-dependent manner.
CHOP mRNA induction is rapidly reversed by leucine
replenishment. Elevated mRNA levels result from both an increase in
the rate of CHOP transcription and an increase in the
CHOP mRNA stability. Using a transient expression
assay, we show that a promoter fragment, when linked to a reporter
gene, is sufficient to mediate the regulation of CHOP
expression by leucine starvation in HeLa cells. In addition, we found
that decreasing amino acid concentration by itself can induce
CHOP expression independently of a cellular stress due to
protein synthesis inhibition. Moreover, CHOP expression is
induced at leucine concentrations in the range of those observed in
blood of protein-restricted animals suggesting that amino acids can
participate, in concert with hormones, in the regulation of gene
expression.
Unité de Nutrition Cellulaire et
Moléculaire, INRA de Theix,
63122 Saint Genès Champanelle, France and 
Skirball
Institute of Biomolecular Medicine, New York University Medical Center,
New York, New York 10016
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