PP2A phosphatase activity is required for stress and Tor kinase regulation of yeast stress response factor Msn2p
PP2A phosphatase activity is required for stress and Tor kinase regulation of yeast stress response factor Msn2p
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DOI：
10.1128/ec.3.5.1261-1271.2004
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发表时间：
2004-10-01
期刊：
影响因子：
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通讯作者：
Garrett, S
中科院分区：
文献类型：
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作者：
Santhanam, A;Hartley, A;Garrett, S
在应激和营养匮乏的情况下，酿酒酵母转录因子Msn2p在细胞核中积累并激活一系列基因的表达。在这里，我们分析了Tor（雷帕霉素靶点）信号通路在介导这些反应中的作用。使用tap42（Ts）等位基因使Tor通路组分Tap42p失活，导致持续的核定位，类似于加入Tor激酶抑制剂雷帕霉素后的情况。Tap42p相互作用蛋白TIP41的缺失可以抑制Tap42p失活和雷帕霉素添加的影响。这些结果支持了雷帕霉素通过使Tap42p功能失活而影响Msn2p的观点。Tap42p与PP2A（蛋白磷酸酶2A）和PP2A样磷酸酶的催化亚基相互作用。在tap42（Ts）菌株和经雷帕霉素处理的野生型菌株中，缺失形成PP2A磷酸酶复合物的催化或调节亚基均可阻止Msn2p的核积累。这些结果表明，Tap42p是PP2A磷酸酶的抑制剂，从而抑制Msn2p的核输出。有趣的是，PP2A功能也需要Msn2p的核积累，以应对应激，如热和渗透休克，以及氮（但不是葡萄糖）饥饿。因此，PP2A和Tor激酶途径将胁迫和氮饥饿信号转导到Msn2p。最后，Msn2p的定位不受14-3-3蛋白功能条件丧失的影响，排除了14-3-3蛋白作为支架在细胞质中隔离Msn2p的可能性。
In response to stress and nutrient starvation, the Saccharomyces cerevisiae transcription factor Msn2p accumulates in the nucleus and activates expression of a broad array of genes. Here, we analyze the role of the Tor (target of rapamycin) signaling pathway in mediating these responses. Inactivation of the Tor pathway component Tap42p using tap42(Ts) alleles causes a sustained nuclear localization similar to that after the addition of the Tor kinase inhibitor rapamycin. Effects of Tap42p inactivation and rapamycin addition could be suppressed by deletion of TIP41, which encodes a Tap42p-interacting protein. These results support the notion that rapamycin affects Msn2p by inactivating Tap42p function. Tap42p interacts with the catalytic subunit of PP2A (protein phosphatase 2A) and PP2A-like phosphatases. Deletion of either the catalytic or regulatory subunit that forms the PP2A phosphatase complex prevents nuclear accumulation of Msn2p in the tap42(Ts) strain and in wild-type strains treated with rapamycin. These results suggest that Tap42p is an inhibitor of PP2A phosphatase, which in turn inhibits nuclear export of Msn2p. Interestingly, PP2A function is also required for nuclear accumulation of Msn2p in response to stresses, such as heat and osmotic shock, as well as nitrogen (but not glucose) starvation. Thus, PP2A and the Tor kinase pathway transduce stress and nitrogen starvation signals to Msn2p. Finally, Msn2p localization is unaffected by conditional loss of 14-3-3 protein function, ruling out the possibility that 14-3-3 proteins act as a scaffold to sequester Msn2p in the cytoplasm.