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Research article

Complexes containing activating transcription factor (ATF)/cAMP-responsive-element-binding protein (CREB) interact with the CCAAT/enhancer-binding protein (C/EBP)–ATF composite site to regulate Gadd153 expression during the stress response

Timothy W. FAWCETT, Jennifer L. MARTINDALE, Kathryn Z. GUYTON, Tsonwin HAI, Nikki J. HOLBROOK
Biochemical Journal Apr 01, 1999, 339 (1) 135-141; DOI: 10.1042/bj3390135
Timothy W. FAWCETT
Gene Expression and Aging Section, Laboratory of Biological Chemistry, NIA, National Institutes of Health, 5600 Nathan Shock Drive, Box 12, Baltimore, MD 21224-6825, U.S.A.
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Jennifer L. MARTINDALE
Gene Expression and Aging Section, Laboratory of Biological Chemistry, NIA, National Institutes of Health, 5600 Nathan Shock Drive, Box 12, Baltimore, MD 21224-6825, U.S.A.
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Kathryn Z. GUYTON
Gene Expression and Aging Section, Laboratory of Biological Chemistry, NIA, National Institutes of Health, 5600 Nathan Shock Drive, Box 12, Baltimore, MD 21224-6825, U.S.A.
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Tsonwin HAI
Ohio State Biochemistry Program, Department of Medical Biochemistry and Neurobiotechnology Center, Ohio State University, Columbus, OH 43210, U.S.A.
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Nikki J. HOLBROOK
Gene Expression and Aging Section, Laboratory of Biological Chemistry, NIA, National Institutes of Health, 5600 Nathan Shock Drive, Box 12, Baltimore, MD 21224-6825, U.S.A.
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  • For correspondence: nikki-holbrook@nih.gov
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Abstract

Gadd153, also known as chop, encodes a member of the CCAAT/enhancer-binding protein (C/EBP) transcription factor family and is transcriptionally activated by cellular stress signals. We recently demonstrated that arsenite treatment of rat pheochromocytoma PC12 cells results in the biphasic induction of Gadd153 mRNA expression, controlled in part through binding of C/EBPβ and two uncharacterized protein complexes to the C/EBP–ATF (activating transcription factor) composite site in the Gadd153 promoter. In this report, we identified components of these additional complexes as two ATF/CREB (cAMP-responsive-element-binding protein) transcription factors having differential binding activities dependent upon the time of arsenite exposure. During arsenite treatment of PC12 cells, we observed enhanced binding of ATF4 to the C/EBP–ATF site at 2 h as Gadd153 mRNA levels increased, and enhanced binding of ATF3 complexes at 6 h as Gadd153 expression declined. We further demonstrated that ATF4 activates, while ATF3 represses, Gadd153 promoter activity through the C/EBP–ATF site. ATF3 also repressed ATF4-mediated transactivation and arsenite-induced activation of the Gadd153 promoter. Our results suggest that numerous members of the ATF/CREB family are involved in the cellular stress response, and that regulation of stress-induced biphasic Gadd153 expression in PC12 cells involves the ordered, sequential binding of multiple transcription factor complexes to the C/EBP–ATF composite site.

  • GADD153 protein
  • gene regulation
  • stress response
  • transcription factors
  • The Biochemical Society, London © 1999
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April 1999

Volume: 339 Issue: 1

Biochemical Journal: 339 (1)
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Complexes containing activating transcription factor (ATF)/cAMP-responsive-element-binding protein (CREB) interact with the CCAAT/enhancer-binding protein (C/EBP)–ATF composite site to regulate Gadd153 expression during the stress response
Timothy W. FAWCETT, Jennifer L. MARTINDALE, Kathryn Z. GUYTON, Tsonwin HAI, Nikki J. HOLBROOK
Biochemical Journal Apr 1999, 339 (1) 135-141; DOI: 10.1042/bj3390135
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Complexes containing activating transcription factor (ATF)/cAMP-responsive-element-binding protein (CREB) interact with the CCAAT/enhancer-binding protein (C/EBP)–ATF composite site to regulate Gadd153 expression during the stress response
Timothy W. FAWCETT, Jennifer L. MARTINDALE, Kathryn Z. GUYTON, Tsonwin HAI, Nikki J. HOLBROOK
Biochemical Journal Apr 1999, 339 (1) 135-141; DOI: 10.1042/bj3390135

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Keywords

GADD153 protein
gene regulation
stress response
transcription factors

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