Regulation of the human stress response gene GADD153 expression: role of ETS1 and FLI-1 gene products.
We have previously shown that ETS transcription factors, regulate cell growth and differentiation, and ETS1 and ETS2 are able to transcriptionally regulate wt p53 gene expression. In the present study we show that the ETS transcription factors also play a role in regulating expression of GADD153, a wt p53 inducible gene, which induces growth arrest and apoptosis in response to stress signals or DNA damage. We report the presence of a single EBS in 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 gene products. In addition, our data show that both ETS1 and FLI-1 strongly activate transcription of the GADD153 EBS linked to the CAT reporter gene. Our 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 proteins provide a novel mechanism of activation for GADD153, allowing these two ETS genes to control its expression during cell growth and differentiation, rather than in response to oxidative stress.
Seth
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A
Medical Research Council Group in Periodontal Physiology and Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario M5S 1B2, Canada.
Giunta
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Franceschil
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Kola
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Venanzoni
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MC
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins; D019556:COS Cells; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D004249:DNA Damage; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D050784:Proto-Oncogene Protein c-ets-1; D051789:Proto-Oncogene Protein c-fli-1; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D050783:Proto-Oncogene Proteins c-ets; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology*; D015533:Transcriptional Activation
D022762:CCAAT-Enhancer-Binding Proteins; C497249:DDIT3 protein, human; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C494041:ETS1 protein, human; D050784:Proto-Oncogene Protein c-ets-1; D051789:Proto-Oncogene Protein c-fli-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D015534:Trans-Activators; D014157:Transcription Factors; D051742:Transcription Factor CHOP; D015500:Chloramphenicol O-Acetyltransferase