ATF3 AND ATF3-DELTA-ZIP - TRANSCRIPTIONAL REPRESSION VERSUS ACTIVATION BY ALTERNATIVELY SPLICED ISOFORMS

ATF3 is a member of the mammalian activating transcription factor/cAMP responsive element binding protein (ATF/CREB) family of transcription factors. In this report, we demonstrate that, contrary to the implica tion of its name, ATF3 represses rather than activates transcription f rom promoters with ATF sites. We also present evidence suggesting that one possible mechanism by which ATF3 represses transcription is to st abilize inhibitory co-factors at the promoter. In addition, we describ e a naturally occurring, alternatively spliced, form of ATF3: ATF3 Del ta Zip. ATF3 Delta Zip lacks the leucine zipper domain and does not bi nd to DNA. In contrast to ATF3, ATF3 Delta Zip stimulates transcriptio n, presumably by sequestering inhibitory co-factors away from the prom oter. It is possible that ATF3 Delta Zip is a physiologically importan t regulator and that it, together with ATF3, regulates the expression of specific target genes.