CHARACTERIZATION OF HUMAN ACTIVATING TRANSCRIPTION FACTOR-4, A TRANSCRIPTIONAL ACTIVATOR THAT INTERACTS WITH MULTIPLE DOMAINS OF CAMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB)-BINDING PROTEIN (CBP)

We demonstrate that human activating transcription factor 4 (hATF4), a member of the activating transcription factor/cAMP-responsive element -binding protein (ATF/CREB) family of transcription factors, is a pote nt transcriptional activator in both mammalian cells and yeast. The N- terminal 113 amino acids of hATF4 activate transcription efficiently, and unexpectedly, the C-terminal bZip DNA binding domain of hATF4 also activates transcription, albeit weakly. Our results indicate that hAT F4 interacts with several general transcription factors: TATA-binding protein, TFIIB, and the RAP30 subunit of TFIIF. In addition, hATF4 int eracts with the coactivator CREB-binding protein (CBP) at four regions : 1) the KIX domain, 2) a region that contains the third zinc finger a nd the E1A-interacting domain, 3) a C-terminal region that contains th e p160/SRC-1-interacting domain, and 4) the recently identified histon e acetyltransferase domain. Interestingly, both the N-terminal and C-t erminal regions of hATF4 interact with the above general transcription factors and CBP, providing a mechanistic explanation for their abilit y to activate transcription. Consistent, with its role as a coactivato r, CBP potentiates the ability of hATF4 to activate transcription. The potential significance of the interaction between hATF4 and multiple factors is discussed.