Transcriptional regulation of the human FasL promoter-enhancer region

Carrie J. Holtz-Heppelmann, Alicia Algeciras, Andrew D. Badley, Carlos V. Paya

Research output: Contribution to journalArticle

130 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4416-4423
Number of pages8
JournalJournal of Biological Chemistry
Volume273
Issue number8
DOIs
StatePublished - Feb 20 1998

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Transcriptional regulation of the human FasL promoter-enhancer region'. Together they form a unique fingerprint.

  • Cite this