CYCLIC AMP-INDEPENDENT ATF FAMILY MEMBERS INTERACT WITH NF-KAPPA-B AND FUNCTION IN THE ACTIVATION OF THE E-SELECTIN PROMOTER IN RESPONSE TOCYTOKINES

Citation
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
Citations number
61
Categorie Soggetti
Biology
ISSN journal
02707306
Volume
13
Issue
11
Year of publication
1993
Pages
7180 - 7190
Database
ISI
SICI code
0270-7306(1993)13:11<7180:CAAFMI>2.0.ZU;2-4
Abstract
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.