Interferon-γ modulates a p53-independent apoptotic pathway and apoptosis-related gene expression

N. K. Ossina, A. Cannas, V. C. Powers, P. A. Fitzpatrick, J. D. Knight, J. R. Gilbert, E. M. Shekhtman, L. D. Tomei, S. R. Umansky, M. C. Kiefer

Research output: Contribution to journalArticlepeer-review

Abstract

Interferon (IFN)-γ increases the sensitivity of tumor cell lines, many of which are p53 mutants, to tumor necrosis factor-α-mediated and anti-Fas antibody-mediated cell death. To better understand the mechanism of IFN-γ action in modulating the cell death response independently of p53 function, we analyzed the death of the human colon adenocarcinoma cell line, HT-29, following treatment with IFN-γ and various cytotoxic agents. Here we show that IFN-γ modulates cell death by sensitizing the cells to killing by numerous pro-apoptotic stimuli but not pro-necrotic stimuli. Furthermore, we show that select genes from several important apoptosis-related gene families are induced by IFN-γ, including the apoptosis-signaling receptors CD95 (Fas/APO-1) and TNFR 1 and interleukin-1β-converting enzyme (Ice) family members Ice, CPP32 (Yama, apopain), ICE(rel)II (TX, Ich-2), Mch-3 (ICE-LAP3, CMH-1), Mch-4, and Mch-5 (MACH, FLICE). Of the bcl-2 family members, IFN-γ directly induced bax but notably not bax, which is activated by p53. The IFN- responsive transcriptional activator interferon regulatory factor-1 was also strongly induced and translocated into the nucleus following IFN-γ treatment. We propose that IFN-γ modulates a p53-independent apoptotic pathway by both directly and indirectly inducing select apoptosis-related genes.

Original languageEnglish
Pages (from-to)16351-16357
Number of pages7
JournalJournal of Biological Chemistry
Volume272
Issue number26
DOIs
Publication statusPublished - 1997

ASJC Scopus subject areas

  • Biochemistry

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