Regulation of the human stress response gene GADD153 expression: role of ETS1 and FLI-1 gene products

We have previously shown that EIS transcription factors, regulate cell grow th and differentiation, and ETS1 and ETS2 are able to transcriptionally reg ulate wt p53 gene expression. In the present study we show that the ETS tra nscription factors also play a role in regulating expression of GADD153, a wt p53 inducible gene, which induces growth arrest and apoptosis in respons e to stress signals or DNA damage. We report the presence of a single EBS i n the human GADD153 promoter, and that the GADD45 gene promoter lacks EBSs, The GADD153 promoter EBS shows a very high affinity for ETS1 and FLI-1 gen e products. In addition, our data show that both ETS1 and FLI-1 strongly ac tivate transcription of the GADD153 EBS linked to the CAT reporter gene. Ou r results also demonstrate how ETS1 and FLI-1 specifically regulate GADD153 expression. In addition, ectopic ETS2 protein expression resulted in only a weak induction of the same CAT reporter construct. The ETS1 and FLI-1 pro teins provide a novel mechanism of activation for GADD153, allowing these t wo ETS genes to control its expression during cell growth and differentiati on, rather than in response to oxidative stress.