gadd153/Chop10, a potential target gene of the transcriptional repressor ATF3

Curt D. Wolfgang, Benjamin P C Chen, Jennifer L. Martindale, Nikki J. Holbrook, Tsonwin Hai

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Abstract

Recently, we demonstrated that the function of ATF3, a stress-inducible transcriptional repressor, is negatively regulated by a bZip protein, gadd153/Chop10. In this report, we present evidence that ATF3 can repress the expression of its own inhibitor, gadd153/Chop10. First, ATF3 represses a chloramphenicol acetyltransferase reporter gene driven by the gadd153/Chop10 promoter when assayed by a transfection assay in vivo and a transcription assay in vitro. Second, the gadd153/Chop10 promoter contains two functionally important binding sites for ATF3: an AP-1 site and a C/EBP-ATF composite site, a previously unidentified binding site for ATF3. The absence of either site reduces the ability of ATF3 to repress the promoter. Third, overexpression of ATF3 by transient transfection results in a reduction of the endogenous gadd153/Chop10 mRNA level. Fourth, as described previously, ATF3 is induced in the liver upon CCl4 treatment. Intriguingly, we show in this report that gadd153/Chop10 mRNA is not present in areas where ATF3 is induced. Taken together, these results strongly suggest that ATF3 represses the expression of gadd153/Chop10. The mutual negative regulation between ATF3 and gadd153/Chop10 is discussed.

Original languageEnglish (US)
Pages (from-to)6700-6707
Number of pages8
JournalMolecular and Cellular Biology
Volume17
Issue number11
StatePublished - Nov 1997

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ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Wolfgang, C. D., Chen, B. P. C., Martindale, J. L., Holbrook, N. J., & Hai, T. (1997). gadd153/Chop10, a potential target gene of the transcriptional repressor ATF3. Molecular and Cellular Biology, 17(11), 6700-6707.