TY - JOUR
T1 - Transcriptional regulation of the human FasL promoter-enhancer region
AU - Holtz-Heppelmann, Carrie J.
AU - Algeciras, Alicia
AU - Badley, Andrew D.
AU - Paya, Carlos V.
PY - 1998/2/20
Y1 - 1998/2/20
N2 - The human FasL enhancer region was cloned and functionally characterized in transformed and primary T cells. Within the 2.3 kilobase pairs of the FasL untranslated region, the distal 3' 300-base pair portion contains a single transcription initiation site and confers basal and inducible transcriptional activity. Stimuli that increase [Ca2+](i) such as CD3 cross-linking or ionomycin, but not activation of protein kinase C, were found to induce FasL enhancer transcription in a cyclosporin-sensitive manner. Moreover, calcineurin and NFAT, but not AP1, were identified as necessary and sufficient effectors in driving FasL transcription through an NFAT cis- acting motif (GGAAA). Additional modes of T cell activation such as CD4 cross-linking were also found to induce NFAT binding to the FasL enhancer region and to functionally transactivate its transcription. These results indicate that the induction of FasL gene transcription in T cells after CD3 or CD4 activation is selectively mediated by calcineurin and N-FAT.
AB - The human FasL enhancer region was cloned and functionally characterized in transformed and primary T cells. Within the 2.3 kilobase pairs of the FasL untranslated region, the distal 3' 300-base pair portion contains a single transcription initiation site and confers basal and inducible transcriptional activity. Stimuli that increase [Ca2+](i) such as CD3 cross-linking or ionomycin, but not activation of protein kinase C, were found to induce FasL enhancer transcription in a cyclosporin-sensitive manner. Moreover, calcineurin and NFAT, but not AP1, were identified as necessary and sufficient effectors in driving FasL transcription through an NFAT cis- acting motif (GGAAA). Additional modes of T cell activation such as CD4 cross-linking were also found to induce NFAT binding to the FasL enhancer region and to functionally transactivate its transcription. These results indicate that the induction of FasL gene transcription in T cells after CD3 or CD4 activation is selectively mediated by calcineurin and N-FAT.
UR - http://www.scopus.com/inward/record.url?scp=0032549017&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032549017&partnerID=8YFLogxK
U2 - 10.1074/jbc.273.8.4416
DO - 10.1074/jbc.273.8.4416
M3 - Article
C2 - 9468493
AN - SCOPUS:0032549017
SN - 0021-9258
VL - 273
SP - 4416
EP - 4423
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 8
ER -