Cyclic AMP-independent ATF family members interact with NF-kappa B and function in the activation of the E-selectin promoter in response to cytokines.
We previously reported that NF-kappa B 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-kappa B in vitro, linking two unrelated families of transcription factors in a novel protein-protein interaction. Furthermore, we demonstrate that the ability of overexpressed NF-kappa B 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-kappa B is, at least in part, the mechanism by which these factors specifically regulate E-selectin promoter activity.
Kaszubska
W
W
Glaxo Institute for Molecular Biology, Geneva, Switzerland.
Hooft van Huijsduijnen
R
R
Ghersa
P
P
DeRaemy-Schenk
A M
AM
Chen
B P
BP
Hai
T
T
DeLamarter
J F
JF
Whelan
J
J
D051696:Activating Transcription Factors; D001483:Base Sequence; D001665:Binding Sites; D001798:Blood Proteins / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics*; D003001:Cloning, Molecular; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D016207:Cytokines / Q000494:pharmacology*; D018076:DNA, Complementary / Q000096:biosynthesis / Q000378:metabolism; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D015723:Gene Library; D005982:Glutathione Transferase / Q000096:biosynthesis / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D016350:Leucine Zippers; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D015345:Oligonucleotide Probes; D010957:Plasmids; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014471:Umbilical Veins
D051696:Activating Transcription Factors; D001798:Blood Proteins; D015815:Cell Adhesion Molecules; D016207:Cytokines; D018076:DNA, Complementary; D019040:E-Selectin; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D015345:Oligonucleotide Probes; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D005576:Colforsin; D000242:Cyclic AMP; D005982:Glutathione Transferase