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A new DAF-16 isoform regulates longevity

机译：新的DAF-16亚型可调节寿命

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摘要

The insulin/IGF-1 signalling (IIS) pathway has diverse roles from metabolism to longevity. In Caenorhabditis elegans, the single forkhead box O (FOXO) homologue, DAF-16, functions as the major target of the IIS pathway. One of two isoforms, DAF-16a, is known to regulate longevity, stress response and dauer diapause. However, it remains unclear how DAF-16 achieves its specificity in regulating these various biological processes. Here we identify a new isoform, DAF-16d/f, as an important isoform regulating longevity. We show that DAF-16 isoforms functionally cooperate to modulate US-mediated processes through differential tissue enrichment, preferential modulation by upstream kinases,rnand regulating distinct and overlapping target genes. Promoter-swapping experiments show both the promoter and the coding region of DAF-16 are important for its function. Importantly, in mammals, four FOXO genes have overlapping and different functions, and in C. elegans, a single FOXO/DAF-16 uses distinct isoforms to fine-tune the US-mediated processes in the context of a whole organism.
机译：胰岛素/ IGF-1信号传导（IIS）途径具有从新陈代谢到长寿的多种作用。在秀丽隐杆线虫中，单个叉头盒O（FOXO）同源物DAF-16是IIS途径的主要靶标。已知两种同工型之一DAF-16a可调节寿命，应激反应和dauer滞育。但是，尚不清楚DAF-16如何在调节这些各种生物过程中达到其特异性。在这里，我们确定了一种新的同工型DAF-16d / f，它是调节寿命的重要同工型。我们显示，DAF-16亚型在功能上合作，通过差异化的组织富集，上游激酶的优先调节，调控独特和重叠的靶基因来调节美国介导的过程。启动子交换实验表明，DAF-16的启动子和编码区对于其功能都很重要。重要的是，在哺乳动物中，四个FOXO基因具有重叠和不同的功能，而在秀丽隐杆线虫中，单个FOXO / DAF-16使用不同的同工型来微调整个生物体中美国介导的过程。

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  • 来源
    《Nature》 |2010年第7305期|P.498-502|共5页
  • 作者

    Eun-Soo Kwon; Sri Devi Narasimhan; Kelvin Yen; Heidi A. Tissenbaum;

  • 作者单位

    Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA;

    rnProgram in Gene Function and Expression, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA;

    rnProgram in Gene Function and Expression, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA;

    rnProgram in Gene Function and Expression, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA Program in Molecular Medicine Universitv of Massachusetts Medical School, Worcester, Massachusetts 01605, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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  • 正文语种 eng
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