Tamura T, Ishihara M, Lamphier M S, Tanaka N, Oishi I, Aizawa S, Matsuyama T, Mak T W, Taki S, Taniguchi T
Department of Immunology, Faculty of Medicine, University of Tokyo, Japan.
Nature. 1995 Aug 17;376(6541):596-9. doi: 10.1038/376596a0.
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 expansion. The tumour suppressor p53 has been shown to regulate this type of apoptosis in thymocytes, but an as yet unknown, p53-independent pathway(s) appears to mediate the same event in mitogen-activated mature T lymphocytes. Here we show DNA damage-induced apoptosis in these T lymphocytes is dependent on the antioncogenic transcription factor interferon regulatory factor (IRF)-1. 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-1 beta converting enzyme (ICE) gene, 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.
淋巴细胞对DNA损伤诱导的凋亡特别敏感，这种反应可能作为一种“利他性自杀”形式，以对抗其固有的高突变和克隆扩增潜力。肿瘤抑制因子p53已被证明可调节胸腺细胞中的这种凋亡类型，但一种尚未明确的、不依赖p53的途径似乎在有丝分裂原激活的成熟T淋巴细胞中介导相同的事件。在这里，我们表明这些T淋巴细胞中DNA损伤诱导的凋亡依赖于抗癌转录因子干扰素调节因子（IRF）-1。因此，T淋巴细胞中不同的凋亡途径需要两种不同的抗癌转录因子p53和IRF-1。我们还表明，白细胞介素-1β转换酶（ICE）基因（秀丽隐杆线虫细胞死亡基因ced-3的哺乳动物同源物）的有丝分裂原诱导是依赖于IRF-1的。IRF-1的异位过表达导致ICE内源性基因的激活，并增强细胞对辐射诱导凋亡的敏感性。
