TY - JOUR
T1 - Role of CREB transcription factor in c-fos activation in natural killer cells
AU - Ponti, Cristina
AU - Gibellini, Davide
AU - Boin, Francesco
AU - Melloni, Elisabetta
AU - Manzoli, Francesco A.
AU - Cocco, Lucio
AU - Zauli, Giorgio
AU - Vitale, Marco
PY - 2002/12/1
Y1 - 2002/12/1
N2 - 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 has a 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-γ, IL-2 and GM-CSF genes.
AB - 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 has a 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-γ, IL-2 and GM-CSF genes.
KW - Cellular activation
KW - NK cell
KW - Transcription factor
UR - http://www.scopus.com/inward/record.url?scp=0036909619&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036909619&partnerID=8YFLogxK
U2 - 10.1002/1521-4141(200212)32:12<3358::AID-IMMU3358>3.0.CO;2-Q
DO - 10.1002/1521-4141(200212)32:12<3358::AID-IMMU3358>3.0.CO;2-Q
M3 - Article
C2 - 12432566
AN - SCOPUS:0036909619
SN - 0014-2980
VL - 32
SP - 3358
EP - 3365
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 12
ER -