Kumar A, Commane M, Flickinger T W, Horvath C M, Stark G R
Department of Molecular Biology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Science. 1997 Nov 28;278(5343):1630-2. doi: 10.1126/science.278.5343.1630.
Signal transducers and activators of transcription (STATs) enhance transcription of specific genes in response to cytokines and growth factors. STAT1 is also required for efficient constitutive expression of the caspases Ice, Cpp32, and Ich-1 in human fibroblasts. As a consequence, STAT1-null cells are resistant to apoptosis by tumor necrosis factor alpha (TNF-alpha). Reintroduction of STAT1alpha restored both TNF-alpha-induced apoptosis and the expression of Ice, Cpp32, and Ich-1. Variant STAT1 proteins carrying point mutations that inactivate domains required for STAT dimer formation nevertheless restored protease expression and sensitivity to apoptosis, indicating that the functions of STAT1 required for these activities are different from those that mediate induced gene expression.
信号转导子和转录激活子（STATs）可响应细胞因子和生长因子增强特定基因的转录。STAT1对于人成纤维细胞中半胱天冬酶Ice、Cpp32和Ich-1的高效组成型表达也是必需的。因此，STAT1基因缺失的细胞对肿瘤坏死因子α（TNF-α）诱导的凋亡具有抗性。重新引入STAT1α可恢复TNF-α诱导的凋亡以及Ice、Cpp32和Ich-1的表达。携带使STAT二聚体形成所需结构域失活的点突变的STAT1变异蛋白仍可恢复蛋白酶表达和对凋亡的敏感性，这表明这些活性所需的STAT1功能不同于介导诱导基因表达的功能。
