Cyclic AMP-independent ATF family members interact with NF-κB and function in the activation of the E-selectin promoter in response to cytokines

Wiweka Kaszubska, Rob Hooft Van Huijsduijnen, Paola Ghersa, Anne Marie Deraemy-Schenk, Benjamin P C Chen, Tsonwin Hai, John F. Delamarter, James Whelan

Research output: Contribution to journalArticle

163 Scopus citations

Abstract

We previously reported that NF-κB and a complex we referred to as NF- ELAM1 play a central role in cytokine-induced expression of the 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 languageEnglish (US)
Pages (from-to)7180-7190
Number of pages11
JournalMolecular and cellular biology
Volume13
Issue number11
DOIs
StatePublished - 1993

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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