Interferon-gamma modulates a p53-independent apoptotic pathway and apoptosis-related gene expression
| Autor: | J D Knight, L D Tomei, M C Kiefer, V C Powers, E M Shekhtman, S R Umansky, N K Ossina, J R Gilbert, Angela Cannas, P A Fitzpatrick |
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| Rok vydání: | 1997 |
| Předmět: |
Programmed cell death
Apoptosis Biology Caspase 8 Biochemistry Interferon-gamma Interferon medicine Humans Interferon gamma RNA Messenger Cycloheximide Molecular Biology Regulation of gene expression Cell Biology Fas receptor Phosphoproteins Cell biology DNA-Binding Proteins IRF1 Gene Expression Regulation Proto-Oncogene Proteins c-bcl-2 Cancer research Tumor Suppressor Protein p53 HT29 Cells medicine.drug Interferon Regulatory Factor-1 |
| Zdroj: | The Journal of biological chemistry. 272(26) |
| ISSN: | 0021-9258 |
| Popis: | Interferon (IFN)-gamma increases the sensitivity of tumor cell lines, many of which are p53 mutants, to tumor necrosis factor-alpha-mediated and anti-Fas antibody-mediated cell death. To better understand the mechanism of IFN-gamma 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-gamma and various cytotoxic agents. Here we show that IFN-gamma 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-gamma, including the apoptosis-signaling receptors CD95 (Fas/APO-1) and TNFR 1 and interleukin-1beta-converting enzyme (Ice) family members Ice, CPP32 (Yama, apopain), ICErel-II (TX, Ich-2), Mch-3 (ICE-LAP3, CMH-1), Mch-4, and Mch-5 (MACH, FLICE). Of the bcl-2 family members, IFN-gamma directly induced bak 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-gamma treatment. We propose that IFN-gamma modulates a p53-independent apoptotic pathway by both directly and indirectly inducing select apoptosis-related genes. |
| Databáze: | OpenAIRE |
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