An alternatively spliced isoform of transcriptional repressor ATF3 and its induction by stress stimuli

Abstract

Activating transcription factor 3 (ATF3) is a member of the ATF/CREB family of transcription factors and its expression is increased by various pathophysiological conditions and in several cancer cells. In this study, we describe two alternatively spliced ATF3DeltaZip mRNAs: ATF3DeltaZip2a and ATF3DeltaZip2b. Both variants encoded the same truncated protein of 135 amino acids, which lacked the leucine zipper domain and was incapable of binding to the ATF/CRE motif. The ATF3DeltaZip2 protein was shown to be localized in the nuclei and counteracted the transcriptional repression by the full-length ATF3. Western blot analysis showed that ATF3DeltaZip2 was expressed in cells exposed to A23187. Further study showed that, similar to the full-length ATF3, the expression of ATF3DeltaZip2 was induced by a wide range of stress stimuli. However, its expression was not detectable in cancer cells that constitutively over-expressed ATF3. Taken together, our results suggest that ATF3DeltaZip2, a protein derived from alternatively spliced mRNAs, is induced by various stress signals and may modulate the activity of the full-length ATF3 protein during stress response.