An IRF-1-dependent pathway of DNA damage-induced apoptosis in mitogen-activated T lymphocytes

Abstract

Lymphocytes are particularly susceptible to DNA damage-induced apoptosis, a response which may serve as a form of ‘altruistic suicide ’ to counter their intrinsic high potential for mutation and clonal expansion1. The tumour suppressor p53 has been shown to regulate this type of apoptosis in thymocytes2,3, but an as yet unknown, p53-independent pathway(s) appears to mediate the same event in mitogen-activated mature T lymphocytes4. Here we show that DNA damage-induced apoptosis in these T lymphocytes is dependent on the antioncogenic transcription factor interferon regulatory factor (IRF)-l (refs 5-7). Thus two different anti-onco-genic transcription factors, p53 and IRF-1, are required for distinct apoptotic pathways in T lymphocytes. We also show that mitogen induction of the interleukin-lβ converting enzyme (ICE) gene8á-10, a mammalian homologue of the Caenorhabditis elegans cell death gene ced-3, is IRF-1-dependent. Ectopic overexpression of IRF-1 results in the activation of the endogenous gene for ICE and enhances the sensitivity of cells to radiation-induced apoptosis. © 1995, Nature Publishing Group. All Rights Reserved.