Expression of Fas ligand in activated T cells is regulated by c-Myc.
The transcription factor c-Myc is important for the control of cell cycle progression, neoplasia, and apoptotic cell death. c-Myc dimerizes with its partner Max to form an active transcription factor complex. Little is known, however, about the transcriptional targets of c-Myc and their roles in c-Myc-induced cell death. Here we demonstrate that T cell activation-induced expression of Fas ligand (FasL, CD95-L, APO-1-L), which can induce apoptotic cell death in many different cell types, is regulated by c-Myc. Down-modulation of c-Myc protein via antisense oligonucleotides blocked activation-induced FasL mRNA and protein expression and functional FasL expression in activated T cells and T cell lines. Further, FasL promoter activity in T cells is driven by overexpression of c-Myc and inhibited by expression of dominant-negative mutants of c-Myc and Max. Our findings indicate that c-Myc controls apoptotic cell death in T cells through regulation of FasL expression.
Brunner
T
T
Division of Immunopathology, Institute for Pathology, University of Berne, 3010 Berne, Switzerland.
Kasibhatla
S
S
Pinkoski
M J
MJ
Frutschi
C
C
Yoo
N J
NJ
Echeverri
F
F
Mahboubi
A
A
Green
D R
DR
D001483:Base Sequence; D001665:Binding Sites; D017931:DNA Primers; D053222:Fas Ligand Protein; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism / Q000502:physiology*; D013601:T-Lymphocytes / Q000378:metabolism*
D017931:DNA Primers; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D016271:Proto-Oncogene Proteins c-myc