TIP41 interacts with TAP42 and negatively regulates the TOR signaling pathway
TIP41 interacts with TAP42 and negatively regulates the TOR signaling pathway
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DOI：
10.1016/s1097-2765(01)00386-0
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发表时间：
2001-11-01
期刊：
影响因子：
16
通讯作者：
Hall, MN
中科院分区：
文献类型：
--
作者：
Jacinto, E;Guo, B;Hall, MN
在酿酒酵母中，雷帕霉素敏感性TOR激酶通过促进2A型相关磷酸酶SIT 4与抑制剂TAP 42的结合来负调节该磷酸酶。在这里，我们描述了TIP41，一个保守的TAP 42相互作用的蛋白参与调节SIT4。TIP41基因的缺失赋予雷帕霉素抗性，抑制TAP 42突变，并防止SIT 4从TAP 42解离。此外，TIP41缺失阻止SIT4依赖性事件，如激酶NPR 1的去磷酸化和转录因子GLN 3的核转位。因此，TIP41通过结合和抑制TAP 42来负调节TOR通路。TIP41与TAP 42的结合在雷帕霉素处理后通过TIP41的SIT 4依赖性去磷酸化而被刺激，这表明TIP41是在TOR失活条件下快速放大SIT 4磷酸酶活性的反馈环的一部分。
In Saccharomyces cerevisiae, the rapamycin-sensitive TOR kinases negatively regulate the type 2A-related phosphatase SIT4 by promoting the association of this phosphatase with the inhibitor TAP42. Here, we describe TIP41, a conserved TAP42-interacting protein involved in the regulation of SIT4. Deletion of the TIP41 gene confers rapamycin resistance, suppresses a tap42 mutation, and prevents dissociation of SIT4 from TAP42. Furthermore, a TIP41 deletion prevents SIT4-dependent events such as dephosphorylation of the kinase NPR1 and nuclear translocation of the transcription factor GLN3. Thus, TIP41 negatively regulates the TOR pathway by binding and inhibiting TAP42. The binding of TIP41 to TAP42 is stimulated upon rapamycin treatment via SIT4-dependent dephosphorylation of TIP41, suggesting that TIP41 is part of a feedback loop that rapidly amplifies SIT4 phosphatase activity under TOR-inactivating conditions.