| Autor: |
TAMURA, Tomohiko, ISHIHARA, Masahiro, LAMPHIER, Marc S., TANAKA, Nobuyuki, OISHI, Isao, AIZAWA, Shinichi, MATSUYAMA, Toshifumi, MAK, Tak W., TAKI, Shinsuke, TANIGUCHI, Tadatsugu |
| Předmět: |
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| Zdroj: |
Leukemia (08876924); Apr97 Supplement 3, Vol. 11, p439-440, 2p |
| Abstrakt: |
Lymphocytes are highly sensitive to DNA damage-induced apoptosis. In thymocytes, the tumor suppressor p53 has been shown to be required for this type of apoptosis. However an as yet unknown, p53-independent pathway(s) appears to mediate the same event in mitogenically activated mature T lymphocytes. By using mice with a null mutation in the IRF-1 gene, we revealed that DNA damage-induced apoptosis in the latter cell type is dependent on the anti-oncogenic transcription factor interferon regulatory factor-1 (IRF-1). Thus two different anti-oncogenic transcription factors, p53 and IRF-1, are required for distinct apoptotic pathways in T lymphocytes. Furthermore, we found that mitogen induction of the interleukin-1β-converting enzyme (Ice) gene, a mammalian homolog of the Caenorhabditis elegans cell death gene ced-3, is also IRF-1-dependent. An IRF-1 binding sequence was identified in the 5' flanking region of the Ice gene. In addition, ectopic overexpression of IRF-1 results in the activation of the endogenous Ice gene and enhances the sensitivity of cells to radiation-induced apoptosis. Thus, induction of lee gene may be involved in IRF-1 dependent DNA damage-induced apoptosis in activated mature T lymphocytes. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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