Transcriptional regulation of Fas gene expression by GA-binding protein and AP-1 in T cell antigen receptor.CD3 complex-stimulated T cells.
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.
Li
X R
XR
Department of General Surgery, Rush Presbyterian St. Luke's Medical Center, Chicago, Illinois 60612, USA.
Chong
A S
AS
Wu
J
J
Roebuck
K A
KA
Kumar
A
A
Parrillo
J E
JE
Rapp
U R
UR
Kimberly
R P
RP
Williams
J W
JW
Xu
X
X
D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051268:GA-Binding Protein Transcription Factor; D005786:Gene Expression Regulation; D006801:Humans; D019169:Jurkat Cells; D020935:MAP Kinase Signaling System; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D019014:fas Receptor
D017252:CD3 Complex; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; C491901:FAS protein, human; D051268:GA-Binding Protein Transcription Factor; D009479:Neuropeptides; D011948:Receptors, Antigen, T-Cell; D018124:Receptors, Tumor Necrosis Factor; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D019014:fas Receptor