Tor and cyclic AMP-protein kinase A: two parallel pathways regulating expression of genes required for cell growth.
Tor and cyclic AMP-protein kinase A: two parallel pathways regulating expression of genes required for cell growth.
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Tor 和环 AMP 蛋白激酶 A：调节细胞生长所需基因表达的两条平行途径。
DOI：
10.1128/ec.4.1.63-71.2005
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Cardenas,MariaE
中科院分区：
文献类型：
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作者：
Zurita-Martinez,SaraA;Cardenas,MariaE
在芽殖酵母酿酒酵母（Saccharomyces cerevisiae）中，Tor和cAMP-蛋白激酶A（cAMP-PKA）信号级联响应营养并协调调节细胞生长所需基因的表达，包括核糖体蛋白（RP）和应激反应（STRE）基因。雷帕霉素对Tor信号传导的抑制导致RP基因的阻遏和STRE基因的诱导。过度激活PKA信号传导的突变赋予对雷帕霉素的抗性并抑制由雷帕霉素施加的RP基因的阻遏。相比之下，PKA的部分失活赋予雷帕霉素超敏性，但仅适度影响RP基因表达。PKA的完全失活损害RP基因的表达，并伴随着增强STRE基因的表达;值得注意的是，这种改变的转录模式仍然对雷帕霉素敏感，因此受到Tor的控制。这些发现说明了Tor和cAMP-PKA信号通路如何响应营养信号，通过两种平行途径来管理细胞生长所需的基因表达，并且它们对我们理解正常和肿瘤哺乳动物细胞中的类似调控网络具有广泛的意义。
In the budding yeastSaccharomyces cerevisiae, the Tor and cyclic AMP-protein kinase A (cAMP-PKA) signaling cascades respond to nutrients and regulate coordinately the expression of genes required for cell growth, including ribosomal protein (RP) and stress-responsive (STRE) genes. The inhibition of Tor signaling by rapamycin results in repression of the RP genes and induction of the STRE genes. Mutations that hyperactivate PKA signaling confer resistance to rapamycin and suppress the repression of RP genes imposed by rapamycin. By contrast, partial inactivation of PKA confers rapamycin hypersensitivity but only modestly affects RP gene expression. Complete inactivation of PKA impairs RP gene expression and concomitantly enhances STRE gene expression; remarkably, this altered transcriptional pattern is still sensitive to rapamycin and thus subject to Tor control. These findings illustrate how the Tor and cAMP-PKA signaling pathways respond to nutrient signals to govern gene expression required for cell growth via two parallel routes, and they have broad implication for our understanding of analogous regulatory networks in normal and neoplastic mammalian cells.