The activator protein 1 (AP-1) transcription factor is composed of heterodimers of the Fos/activating transcription factor (ATF) and Jun subfamilies of basic-region leucine-zipper (B-ZIP) proteins. In order to determine the identities of individual B-ZIP proteins in various AP-1 complexes we tested the effect of dominant-negative mutants to the B-ZIP proteins c-Fos, ATF2, ATF4 and CCAAT-enhancer-binding protein (C/EBP) on the activities of the collagenase and c-Jun promoters. These dominant-negative mutants inhibit DNA binding of wild-type B-ZIP proteins in a leucine-zipper-dependent fashion. Transcription of a collagenase promoter/reporter gene was induced in HepG2 hepatoma cells by expression of c-Fos and c-Jun, administration of PMA (‘TPA’) or by expression of a truncated form of MEK (mitogen-activated/extracellular-signal-regulated kinase kinase) kinase-1, MEKK1Δ. In all cases, the dominant-negative mutants A-Fos and A-ATF2 decreased collagenase promoter activity. However, A-ATF4 and A-C/EBP had no effect. A-Fos and A-ATF2 also reduced MEKK1Δ-induced stimulation of the c-Jun promoter. In contrast, constitutive c-Jun promoter activity was blocked solely by A-ATF2, strongly suggesting that ATF2 and/or an ATF2-dimerizing protein are of major importance for c-Jun transcription in unstimulated cells. These results demonstrate that AP-1 transcription factors of different compositions control c-jun gene transcription in resting or stimulated cells.
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December 2001
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Research Article|
December 10 2001
Regulation and composition of activator protein 1 (AP-1) transcription factors controlling collagenase and c-Jun promoter activities
Lars STEINMÜLLER;
Lars STEINMÜLLER
∗Department of Medical Biochemistry and Molecular Biology, Building 44, University of Saarland, D-66421 Homburg, Germany
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Giuseppe CIBELLI;
Giuseppe CIBELLI
∗Department of Medical Biochemistry and Molecular Biology, Building 44, University of Saarland, D-66421 Homburg, Germany
†Department of Pharmacology and Human Physiology, Medical Faculty, University of Bari, I-70124 Bari, Italy
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Jonathan R. MOLL;
Jonathan R. MOLL
‡Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, U.S.A.
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Charles VINSON;
Charles VINSON
‡Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, U.S.A.
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Gerald THIEL
Gerald THIEL
1
∗Department of Medical Biochemistry and Molecular Biology, Building 44, University of Saarland, D-66421 Homburg, Germany
1To whom correspondence should be addressed (e-mail bcgthi@uniklinik-saarland.de).
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Publisher: Portland Press Ltd
Received:
May 17 2001
Revision Received:
August 30 2001
Accepted:
September 28 2001
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2001
2001
Biochem J (2001) 360 (3): 599–607.
Article history
Received:
May 17 2001
Revision Received:
August 30 2001
Accepted:
September 28 2001
Citation
Lars STEINMÜLLER, Giuseppe CIBELLI, Jonathan R. MOLL, Charles VINSON, Gerald THIEL; Regulation and composition of activator protein 1 (AP-1) transcription factors controlling collagenase and c-Jun promoter activities. Biochem J 15 December 2001; 360 (3): 599–607. doi: https://doi.org/10.1042/bj3600599
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