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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The PTEN tumor suppressor homolog in Caenorhabditis elegans regulates longevity and dauer formation in an insulin receptor-like signaling pathway
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The PTEN tumor suppressor homolog in Caenorhabditis elegans regulates longevity and dauer formation in an insulin receptor-like signaling pathway

机译：秀丽隐杆线虫中的PTEN抑癌同源物调节胰岛素受体样信号通路中的寿命和dauer形成

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Inactivation of the tumor suppressor PTEN gene is found in a variety of human cancers and in cancer predisposition syndromes. Recently, PTEN protein has been , shown to possess phosphatase activity on phosphatidylinositol 3,4,5-trisphosphate, a product of phosphatidylinositol 3-kinase. We have identified a homolog of PTEN in Caenorhabditis elegans and have found that it corresponds to the daf-18 gene, which had been defined by a single, phenotypically weak allele, daf- 18(e1375). By analyzing an allele, daf-18(nr2037), which bears a deletion of the catalytic portion of CePTEN/DAF-18, we have shown that mutation in daf-18 can completely suppress the dauer-constitutive phenotype caused by inactivation of daf-2 or age-1, which encode an insulin receptor-like molecule and the catalytic subunit of phosphatidylinositol 3-kinase, respectively. In addition, daf-18(nr2037) dramatically shortens lifespan, both in a wild-type background and in a daf-2 mutant background that normally prolongs lifespan. The lifespan in a daf-18(nr2037) mutant can be restored to essentially that of wild type when combined with a daf-2 mutation. Our studies provide genetic evidence that in C elegans, the PTEN homolog DAF-18 functions , as a negative regulator of the DAF-2 and AGE-1 signaling pathway, consistent with the notion that DAF-18 acts a phos- phatidylinositol 3,4,5-trisphosphate phosphatase in vivo. Fur- thermore, our studies have uncovered a longevity-promoting activity of the PTEN homolog in C elegans.
机译：在多种人类癌症和癌症易感综合征中发现了抑癌基因PTEN基因的失活。最近，已显示PTEN蛋白对磷脂酰肌醇3-激酶的产物磷脂酰肌醇3,4,5-三磷酸具有磷酸酶活性。我们在秀丽隐杆线虫中鉴定了PTEN的同源物，并发现它与daf-18基因相对应，该基因已由一个表型较弱的等位基因daf-18（e1375）定义。通过分析携带CePTEN / DAF-18催化部分缺失的等位基因daf-18（nr2037），我们发现daf-18中的突变可以完全抑制daf-失活引起的dauer组成型。 2或age-1，分别编码胰岛素受体样分子和磷脂酰肌醇3-激酶的催化亚基。此外，daf-18（nr2037）在野生型背景和通常会延长寿命的daf-2突变体背景下均会显着缩短寿命。当与daf-2突变结合时，daf-18（nr2037）突变体的寿命可以恢复为野生型。我们的研究提供了遗传证据，表明在秀丽隐杆线虫中，PTEN同源物DAF-18充当DAF-2和AGE-1信号通路的负调节剂，与DAF-18发挥磷脂酰肌醇3,4的观点一致。体内的5-5-三磷酸磷酸酶。此外，我们的研究发现线虫中PTEN同源物具有延长寿命的活性。

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