Kim Hun Sik, Lee Myung-Shik
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Cell Signal. 2007 Mar;19(3):454-65. doi: 10.1016/j.cellsig.2006.09.003. Epub 2006 Sep 30.
Signal transducers and activators of transcription (STATs) are latent cytoplasmic transcription factors that mediate various biological responses, including cell proliferation, survival, apoptosis, and differentiation. Among the members of the STAT family, accumulating evidence now indicates an important role for STAT1 in various forms of cell death. Depending upon stimuli or cell types, STAT1 can modulate a broad spectrum of cell death, comprising both apoptotic and non-apoptotic pathways. STAT1-dependent regulation of cell death is largely dependent on a transcriptional mechanism such as the activation of death-promoting genes. However, non-transcriptional mechanisms such as STAT1 interaction with TRADD, p53, or HDAC have been implicated in the regulation of cell death by STAT1. Furthermore, STAT1 itself is also subject to complex forms of regulation such as post-translational protein modification, which can critically affect STAT1 signaling and STAT1-dependent cell death. Given the reports showing that dysregulation of STAT1 signaling is associated with various pathological conditions, including the development of cancer, a better understanding of the mechanism underlying STAT1 regulation of cell death may lead to successful strategies for targeting STAT1 in such pathological settings.
信号转导子和转录激活子（STATs）是潜在的细胞质转录因子，介导多种生物学反应，包括细胞增殖、存活、凋亡和分化。在STAT家族成员中，越来越多的证据表明STAT1在各种形式的细胞死亡中起重要作用。根据刺激因素或细胞类型，STAT1可以调节广泛的细胞死亡，包括凋亡和非凋亡途径。STAT1依赖的细胞死亡调节很大程度上依赖于转录机制，如促死亡基因的激活。然而，非转录机制，如STAT1与TRADD、p53或HDAC的相互作用，也参与了STAT1对细胞死亡的调节。此外，STAT1本身也受到复杂形式的调节，如翻译后蛋白质修饰，这可能会严重影响STAT1信号传导和STAT1依赖的细胞死亡。鉴于有报道表明STAT1信号失调与包括癌症发展在内的各种病理状况相关，更好地理解STAT1调节细胞死亡的机制可能会带来在这些病理环境中靶向STAT1的成功策略。
