CHOP/GADD153 gene expression response to cellular stresses inhibited by prior exposure to ultraviolet light wavelength band C (UVC) - Inhibitory sequence mediating the UVC response localized to exon 1

CHOP/GADD153 is both an activating and repressing transcription factor that is markedly induced in response to a variety of cellular stresses. The CHOP/ GADD153 gene was originally cloned because of its inducibility by ultraviolet light wavelength band C UVC and has since been found to be activated in response to many different cellular stresses. Some of the recent studies have questioned the UVC responsiveness of the CHOP gene. Contradiction in our own data led us to reexamine the WC effects on CHOP expression. WC is capable of strongly activating the mouse CHOP promoter in stably transfected NIH 3T3 cells but has only a modest and transient effect on the level of the CHOP messenger RNA. In addition to its positive effect on CHOP promoter activity, we show that UVC negatively affects CHOP mRNA and protein expression. Pretreatment of NIH 3T3 cells with WC markedly attenuates the subsequent induction of CHOP mRNA by the cellular stress activators methylmethane sulfate, tunicamycin, glucose deprivation, and methionine deprivation for as long as at least 16 h. This inhibitory effect of UVC on CHOP expression in response to stress is independent of the presence or absence of p53 and does not involve mRNA degradation as opposed to the WC effect that inhibits p21 expression seen only in the absence of p53. The target of the inhibitory effect of WC on CHOP expression is located in the first exon of the gene, a 5'-untranslated region that is unusually conserved between different species. These findings suggest that an unknown function encoded by the 5'-untranslated region somehow modifies the response of CHOP gene transcription to WC.