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Originally published In Press as doi:10.1074/jbc.M201959200 on April 17, 2002
J. Biol. Chem., Vol. 277, Issue 27, 24120-24127, July 5, 2002
ATF4 Is a Mediator of the Nutrient-sensing Response Pathway That
Activates the Human Asparagine Synthetase Gene*
Fai
Siu,
Perry J.
Bain,
Rene
LeBlanc-Chaffin,
Hong
Chen, and
Michael S.
Kilberg
From the Department of Biochemistry and Molecular Biology,
Center for Mammalian Genetics, and Center for Nutritional Sciences,
University of Florida College of Medicine, Gainesville, Florida
32610-0245
Transcription from the asparagine synthetase
(A.S.) gene is increased in response to either amino acid
(amino acid response) or glucose (endoplasmic reticulum stress
response) deprivation. These two independent pathways converge on the
same set of genomic cis-elements within the
A.S. promoter referred to as nutrient-sensing response
elements (NSRE) 1 and 2, both of which are necessary for gene
activation. The NSRE-1 sequence was used to screen ATF/CREB family
members by electrophoresis mobility shift assays and supershift by specific antibodies. The results indicated that ATF4 binds to the
NSRE-1 sequence and that the amount of the ATF4 complex was increased
when extracts from amino acid-deprived or glucose-deprived cells were
tested. Using electrophoresis mobility shift assay experiments and a
probe that contained both NSRE-1 and NSRE-2, mutation of the NSRE-1
sequence completely prevented formation of the ATF4-containing
complexes, whereas mutation of the NSRE-2 sequence did not.
Overexpression of ATF4 increased A.S. promoter-driven transcription, whereas an inhibitory dominant negative ATF4 mutant blocked both basal and starvation-enhanced transcription. Collectively, the results provide both in vitro and in vivo
evidence for a role of ATF4 in the transcriptional activation of the
A.S. gene in response to nutrient deprivation.
*
This research was supported by Grant DK-52064 (to
M. S. K.) from the NIDDK, the National Institutes of Health.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of Biochemistry
and Molecular Biology, University of Florida College of Medicine, Box
100245, Gainesville, FL 32610-0245. Tel.: 352-392-2711; Fax:
352-392-6511; E-mail: mkilberg@ufl.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

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|
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[Full Text]
[PDF]
|
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|

|
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|
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277(50):
48107 - 48114.
[Abstract]
[Full Text]
[PDF]
|
 |
|
Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.
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