We previously reported that NF-κB and a complex we referred to as NF-ELAM1 play a central role in cytokine-induced expression of tbe E-selectin gene. In this study we identify cyclic AMP (cAMP)-independent members of the ATF family binding specifically to the NF-ELAM1 promoter element. The NF-ELAM1 element (TGACATCA) differs by a single nucleotide substitution from the cAMP-responsive element consensus sequence. We demonstrate that this sequence operates in a cAMP-independent manner to induce transcription and thus define it as a non-cAMP-responsive element (NCRE). We show that ATFa is a component of the NF-ELAM1 complex and its overexpression activates the E-selectin promoter. In addition, ATFa, ATF2, and ATF3 interact directly with NF-κB in vitro, linking two unrelated families of transcription factors in a novel protein-protein interaction. Furthermore, we demonstrate that the ability of overexpressed NF-κB to transactivate the E-selectin promoter in vivo is dependent on the NF-ELAM1 complex. Our results suggest that a direct interaction between ATFs and NF-κB is, at least in part, the mechanism by which these factors specifically regulate E-selectin promoter activity.
|Original language||English (US)|
|Number of pages||11|
|Journal||Molecular and Cellular Biology|
|Publication status||Published - Nov 1993|
ASJC Scopus subject areas
- Cell Biology
- Molecular Biology