Multiple roles of Tap42 in mediating rapamycin-induced transcriptional changes in yeast
Multiple roles of Tap42 in mediating rapamycin-induced transcriptional changes in yeast
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DOI：
10.1016/s1097-2765(03)00228-4
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发表时间：
2003-06-01
期刊：
影响因子：
16
通讯作者：
Broach, JR
中科院分区：
文献类型：
--
作者：
Düvel, K;Santhanam, A;Broach, JR
Tor蛋白是抗肿瘤药物雷帕霉素的靶点，介导真核生物细胞生长和增殖所需的保守信号通路。通过对酿酒酵母的全局转录分析，我们研究了Tor对酿酒酵母转录调控的重要蛋白Tap 42的作用。我们发现Tap 42的失活，就像雷帕霉素的加入一样，抑制了应激反应基因的激活。相反，Tap 42的失活，以及蛋白磷酸酶Sit 4和Pph 21/22的失活，阻断了雷帕霉素对氮歧视途径基因的诱导。Tap 42失活既不影响核糖体蛋白基因的表达，也不阻断雷帕霉素诱导的这些基因的抑制。这些结果表明，Tap 42可以抑制和激活蛋白磷酸酶，并提供深入了解TOR转录调控的复杂事件。
Tor proteins, targets of the antiinflammatory drug rapamycin, mediate a conserved signaling pathway required for cell growth and proliferation in eukaryotes. By global transcriptional analysis of Saccharomyces cerevisiae, we have examined the role of the essential protein Tap42 in transcriptional regulation by Tor. We find that Tap42 inactivation, like rapamycin addition, prolongs activation of stress response genes. In contrast, Tap42 inactivation, as does inactivation of the protein phosphatases Sit4 and Pph21/22, blocks rapamycin induction of nitrogen discrimination pathway genes. Tap42 inactivation neither affects ribosomal protein gene expression nor blocks rapamycin-induced repression, of these genes. These results indicate that Tap42 can both inhibit and activate protein phosphatases and provide insight into the complex events underlying TOR regulation of transcription.