gadd153/Chop10, a potential target gene of the transcriptional repressor ATF3.
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.
Wolfgang
C D
CD
Ohio State Biochemistry Program, Ohio State University, Columbus 43210, USA.
Chen
B P
BP
Martindale
J L
JL
Holbrook
N J
NJ
Hai
T
T
D051700:Activating Transcription Factor 3; D051696:Activating Transcription Factors; D000818:Animals; D001665:Binding Sites; D001798:Blood Proteins; D022762:CCAAT-Enhancer-Binding Proteins; D002251:Carbon Tetrachloride / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D016350:Leucine Zippers; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051381:Rats; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018808:Transcription Factor AP-1; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic
D051700:Activating Transcription Factor 3; D051696:Activating Transcription Factors; C497108:Atf3 protein, rat; D001798:Blood Proteins; D022762:CCAAT-Enhancer-Binding Proteins; C497249:DDIT3 protein, human; D004268:DNA-Binding Proteins; C497251:Ddit3 protein, rat; D009687:Nuclear Proteins; D012097:Repressor Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D051742:Transcription Factor CHOP; D002251:Carbon Tetrachloride