title: Role of CREB transcription factor in c-fos activation in natural killer cells.
abstract: In natural killer (NK) cells, interleukin-2 (IL-2) differentially regulates the expression of several transcription factors, including JunB and c-fos. The cAMP response element binding protein, CREB, is a key transcriptional regulator of a large number of genes containing the octanucleotide CRE consensus sequence in their upstream regulatory regions. We studied here the functional role of CREB in the IL-2-mediated transcriptional regulation of c-fos in human NK cells. Our results show that IL-2 activates CREB in human NK cells and that CREB activation hasa prominent regulatory role on the IL-2-induced expression of functional c-fos and AP-1 in NK cells. We identify two domains of the c-fos promoter, containing three CRE sites, which are critical for the transcriptional activity induced by IL-2. The first domain is located within the first 220 nucleotides of the c-fos promoter, while the second encompasses the nucleotides - 440 and - 220. Our results show that CREB has a relevant role in the cytokine-mediated activation of NK cells, and are particularly remarkable in the light of the several genes that are positively regulated by c-fos and AP-1, such as IFN-gamma, IL-2 and GM-CSF genes.
authors.affiliation: Department of Anatomical Sciences, Cellular Signalling Laboratory, University of Bologna, Bologna, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ponti
authors.forename: Davide
authors.initials: D
authors.lastname: Gibellini
authors.forename: Francesco
authors.initials: F
authors.lastname: Boin
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Melloni
authors.forename: Francesco A
authors.initials: FA
authors.lastname: Manzoli
authors.forename: Lucio
authors.initials: L
authors.lastname: Cocco
authors.forename: Giorgio
authors.initials: G
authors.lastname: Zauli
authors.forename: Marco
authors.initials: M
authors.lastname: Vitale
mesh_terms: D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000737:chemistry / Q000378:metabolism*; D016762:Genes, fos; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D007376:Interleukin-2; D016760:Proto-Oncogene Proteins c-fos; D011994:Recombinant Proteins