Cell growth arrest and induction of cyclin-dependent kinase inhibitor p21(WAF1/CIP1) mediated by STAT1
Cell growth arrest and induction of cyclin-dependent kinase inhibitor p21(WAF1/CIP1) mediated by STAT1
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DOI：
10.1126/science.272.5262.719
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发表时间：
1996-05-03
期刊：
影响因子：
56.9
通讯作者：
Fu, XY
中科院分区：
文献类型：
--
作者：
Chin, YE;Kitagawa, M;Fu, XY
信号转导和转录激活因子（STAT）蛋白可以在响应表皮生长因子（EGF）和干扰素(IFN)- γ时被条件激活。STAT激活与EGF和ifn - γ对细胞生长的抑制相关。活化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应答元件，并调节p21信使RNA的诱导。ifn - γ不抑制缺乏STAT1的U3A细胞的生长，但抑制重新引入STAT1 α的U3A细胞的生长。因此，STAT1蛋白对于ifn - γ对细胞生长的抑制至关重要。STAT信号通路似乎通过诱导CDK抑制剂响应细胞因子来负性调节细胞周期。
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.