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J Biol Chem, Vol. 274, Issue 20, 14079-14089, May 14, 1999
Down-regulation of Tumor Necrosis Factor Expression by
Activating Transcription Factor 2 Increases UVC-induced Apoptosis of
Late-stage Melanoma Cells
Vladimir N.
Ivanov and
Ze'ev
Ronai
From the Ruttenberg Cancer Center, Mount Sinai School of Medicine,
New York, New York 10029-6574
To identify mechanisms whereby activating
transcription factor 2 (ATF2) alters the radiation resistance of human
melanoma cells, we examined the possible role of ATF2 in UVC-induced
apoptosis. Forced expression of full-length or truncated ( 1-195
amino acids) forms of ATF2 in LU1205, a late-stage human melanoma cell
line, elevated the levels of UVC-induced apoptosis. At the same time, either truncated or full-length forms of ATF2 reduced UVC-induced activation of the tumor necrosis factor- (TNF ) promoter and decreased expression of TNF . Forced expression of c-Jun in
ATF2-expressing melanoma cells restored TNF expression, suggesting
that both forms of ATF2 sequestered transcription factors that
positively regulate TNF expression in response to UV irradiation.
Antagonistic antibodies to Fas, but not to TNFR1, efficiently
suppressed UVC-induced apoptosis, suggesting that the Fas pathway
mediates the primary apoptotic signal in melanoma cells whereas the
TNFR1 pathway elicits a survival signal. Indeed, treatment of melanoma
cells with TNF before UVC irradiation partially suppressed
UVC-induced apoptosis, further supporting the protective role of TNF
in UVC-treated melanoma cells. Taken together, our findings suggest
that ATF2 contributes to UVC-induced apoptosis through transcriptional
silencing of TNF , which balances Fas-mediated cell death in melanoma.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 1999 by the American Society for Biochemistry and Molecular Biology.
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