Transcriptional regulation of Fas gene expression by GA-binding protein and AP-1 in T cell antigen receptor · CD3 complex-stimulated T cells

Xiao Rui Li, Anita S.F. Chong, Jianming Wu, Kenneth A. Roebuck, Aseem Kumar, Joseph E. Parrillo, Ulf R. Rapp, Robert P. Kimberly, James W. Williams, Xiulong Xu

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

Fas (CD95 or APO-1), a transmembrane cell surface receptor of the tumor necrosis factor receptor family, is up-regulated in activated T lymphocytes. Our present study identified an upstream enhancer element (between nucleotide positions -862 and -682) containing a GA-binding protein (GABP) site and a low affinity activating protein-1 (AP-1)-binding site. T cell activation increased the DNA binding of GABP and AP-1 to this enhancer site. The specificity of GABP and AP-1 binding was demonstrated by competition electrophoretic mobility shift assay and supershift electrophoretic mobility shift assay with antibodies against GABP and AP-1, respectively. Mutational analysis of Fas promoter revealed that both GABP- and AP-1-binding sites were required for initiating Fas gene transcription. We further show that anti-CD3 mAb, phorbol 12-myristate 13-acetate, and phorbol 12-myristate 13- acetate/ionomycin strongly activated promoters carrying multiple copies of the Fas enhancer, and mutation of either the GABP or AP-1 binding site severely reduced transcriptional activity. Taken together, these results suggest that the transcription factors GABP and AP-1 play a critical role in the induction of Fas gene expression in T cell antigen receptor-CD3- stimulated Jurkat cells.

Original languageEnglish (US)
Pages (from-to)35203-35210
Number of pages8
JournalJournal of Biological Chemistry
Volume274
Issue number49
DOIs
StatePublished - Dec 3 1999

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