GADD153 CHOP10, A POTENTIAL TARGET GENE OF THE TRANSCRIPTIONAL REPRESSOR ATF3/

Recently, we demonstrated that the function of ATF3, a stress-inducibl e transcriptional repressor, is negatively regulated by a bZip protein , gadd153/Chop10. In this report, we present evidence that ATF3 can re press 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 v ivo and a transcription assay in vitro, Second, the gadd153/Chop10 pro moter contains two functionally important binding sites for ATF3: an A P-1 site and a C/EBP-ATF composite site, a previously unidentified bin ding site for ATF3, The absence of either site reduces the ability of ATF3 to repress the promoter, Third, overexpression of ATF3 by transie nt transfection results in a reduction of the endogenous gadd153/Chop1 0 mRNA level. Fourth, as described previously, ATM is induced in the l iver upon CCl4 treatment. Intriguingly, we show in this report that ga dd153/Chop10 mRNA is not present in areas where ATF3 is induced, Taken together, these results strongly suggest that ATF3 represses the expr ession of gadd153/Chop10. The mutual negative regulation between ATF3 and gadd153/Chop10 is discussed.