Stephanou Anastasis, Latchman David S
Medical Molecular Biology Unit, Institute of Child Health, University College London, London, UK.
Int J Exp Pathol. 2003 Dec;84(6):239-44. doi: 10.1111/j.0959-9673.2003.00363.x.
Extracellular signalling molecules binding to their specific receptors are able to modulate gene expression, leading to changes in development, cell growth and homeostasis. The signal transducers and activators of transcription (STAT) protein family members are among the best studied of the latent cytoplasmic signal-dependent transcription factors. The STAT factors are activated via phosphorylation on the C-terminal domain following cytokine signalling or by various stress-induced stimuli. Recently, STAT-1 has been implicated in modulating pro- and anti-apoptotic genes following several stress-induced responses. These effects are dependent on STAT-1 phosphorylation on serine-727 and require the C-terminal transactivation domain of STAT-1 to enhance its pro-apoptotic effect or inhibit its anti-apoptotic effects. The STAT-1 C-terminal domain has been demonstrated to be important for protein-protein interaction with other transcriptional activators. The reports that STAT-1-deficient mice develop spontaneous and chemically induced tumours more rapidly compared to wild-type mice and that STAT-1-deficient cells are more resistant to agents that induce apoptosis strongly support the argument that STAT-1 acts as a tumour suppressor.
与特定受体结合的细胞外信号分子能够调节基因表达，从而导致发育、细胞生长和体内平衡的变化。信号转导及转录激活蛋白（STAT）家族成员是研究最为深入的潜在细胞质信号依赖性转录因子之一。STAT因子在细胞因子信号传导后通过C末端结构域的磷酸化或各种应激诱导刺激而被激活。最近，STAT-1在几种应激诱导反应后参与调节促凋亡和抗凋亡基因。这些效应依赖于STAT-1丝氨酸727位点的磷酸化，并且需要STAT-1的C末端反式激活结构域来增强其促凋亡作用或抑制其抗凋亡作用。已证明STAT-1的C末端结构域对于与其他转录激活因子的蛋白质-蛋白质相互作用很重要。与野生型小鼠相比，STAT-1缺陷型小鼠更快速地发生自发性和化学诱导性肿瘤，并且STAT-1缺陷型细胞对诱导凋亡的药物更具抗性，这些报道有力地支持了STAT-1作为肿瘤抑制因子的观点。
