W. Kaszubska et al., CYCLIC AMP-INDEPENDENT ATF FAMILY MEMBERS INTERACT WITH NF-KAPPA-B AND FUNCTION IN THE ACTIVATION OF THE E-SELECTIN PROMOTER IN RESPONSE TOCYTOKINES, Molecular and cellular biology, 13(11), 1993, pp. 7180-7190
We previously reported that NF-kappaB and a complex we referred to as
NF-ELAM1 play a central role in cytokine-induced expression of the E-s
electin gene. In this study we identify cyclic AMP (cAMP)-independent
members of the ATF family binding specifically to the NF-ELAM1 promote
r element. The NF-ELAM1 element (TGACATCA) differs by a single nucleot
ide substitution from the cAMP-responsive element consensus sequence.
We demonstrate that this sequence operates in a cAMP-independent manne
r 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 compl
ex and its overexpression activates the E-selectin promoter. In additi
on, ATFa, ATF2, and ATF3 interact directly with NF-kappaB in vitro, li
nking two unrelated families of transcription factors in a novel prote
in-protein interaction. Furthermore, we demonstrate that the ability o
f overexpressed NF-kappaB 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-kappaB is, at least in part, th
e mechanism by which these factors specifically regulate E-selectin pr
omoter activity.