ATF-A0, A NOVEL VARIANT OF THE ATF CREB TRANSCRIPTION FACTOR FAMILY, FORMS A DOMINANT TRANSCRIPTION INHIBITOR IN ATF-A HETERODIMERS/

We have isolated a cDNA encoding a variant of the transcription factor ATF-a (called ATf-a0) by screening a HeLa cDNA expression library wit h a regulatory element of the E-selectin promoter, NF-ELAM1/deltaA. Re lative to full-length ATF-a, the ATF-a0 cDNA contains a large in-frame deletion of 525 base pairs that removes the P/S/T-rich putative trans activation domain. Using reverse-transcription-polymerase chain reacti on and Northern blot hybridization to characterize ATF-a0 expression, we found that putative mRNAs for ATF-a0 and ATF-a are present at varyi ng ratios in different tissues. Full-length ATF-a is a transcriptional activator for the NF-ELAM1/deltaA site of the E-selectin promoter. In contrast, we show ATF-a0 has no measurable transactivating function o n this element. Moreover, we demonstrate that co-expressed ATF-a0 and ATF-a preferentially heterodimerize. In the heterodimer ATF-a0 is a do minant inhibitor that completely blocks the transactivating activity o f ATF-a. Both forms of ATF-a bind the p50 subunit of NF-kappaB as show n by affinity chromatography. ATF-a0 appears to be a splice variant si milar to the one found for ATF-2, its closest homologue in structure a nd function. Taken together, our results suggest that ATF-a0 is an imp ortant member of the ATF family with a negative regulatory role in tra nsactivation.