Murine activating transcription factor 3 is induced by hypoxia through multiple cis-acting elements including p53 sites
ATF3 is an immediate-early gene and a member of the bZip family of transcription factors. In many different cell types ATF3 expression is rapidly and transiently induced in response to two distinct stimuli, growth signals and stressors. A number of different target genes include those involved in cell cycle control, apoptosis, and energy metabolism. In this thesis it is reported that ATF3 mRNA and protein are strongly and transiently induced in response to hypoxia in two different cell types. Analysis of the murine ATF3 promoter revealed that a number of potential hypoxia response elements do not participate in the hypoxia response. However, these studies revealed that two p53 sites contribute to hypoxic induction. Furthermore, a single CRE site within the promoter contributes to basal repression of the ATF3 promoter. Finally, ATF3 expression is observed to co-localize with areas of hypoxia in HCT 116 xenograft tumours produced in mice.