Chin Y E, Kitagawa M, Su W C, You Z H, Iwamoto Y, Fu X Y
Department of Pathology, Yale University School of Medicine, New Haven, CT 06520-8023, USA.
Science. 1996 May 3;272(5262):719-22. doi: 10.1126/science.272.5262.719.
Signal transducers and activators of transcription (STAT) proteins can be conditionally activated in response to epidermal growth factor (EGF) and interferon (IFN)-gamma. STAT activation was correlated with cell growth inhibition in response to EGF and IFN-gamma. Activated STAT proteins specifically recognized the conserved STAT-responsive elements in the promoter of the gene encoding the cyclin-dependent kinase (CDK) inhibitor p21 WAF1/CIP1 and regulated the induction of p21 messenger RNA. IFN-gamma did not inhibit the growth of U3A cells, which are deficient in STAT1, but did inhibit the growth of U3A cells into which STAT1 alpha was reintroduced. Thus, STAT1 protein is essential for cell growth suppression in response to IFN-gamma. The STAT signaling pathway appears to negatively regulate the cell cycle by inducing CDK inhibitors in response to cytokines.
信号转导子和转录激活子（STAT）蛋白可根据表皮生长因子（EGF）和干扰素（IFN）-γ而被有条件地激活。STAT激活与对EGF和IFN-γ的细胞生长抑制相关。激活的STAT蛋白特异性识别编码细胞周期蛋白依赖性激酶（CDK）抑制剂p21 WAF1/CIP1的基因启动子中的保守STAT反应元件，并调节p21信使核糖核酸的诱导。IFN-γ不抑制STAT1缺陷的U3A细胞的生长，但可抑制重新导入STAT1α的U3A细胞的生长。因此，STAT1蛋白对于响应IFN-γ的细胞生长抑制至关重要。STAT信号通路似乎通过响应细胞因子诱导CDK抑制剂而对细胞周期进行负调控。
