Fission yeast is a good model organism for the study of lifespan. To elucidate the mechanism, we screened for long-lived mutants. We found a nonsense mutation in the ksg1⁺ gene, which encodes an ortholog of mammalian PDK1 (phosphoinositide-dependent protein kinase). The mutation was in the PH domain of Ksg1 and caused defect in membrane localization and protein stability. Analysis of the ksg1 mutant revealed that the reduced amounts and/or activity of the Ksg1 protein are responsible for the increased lifespan. Ksg1 is essential for growth and known to phosphorylate multiple substrates, but the substrate responsible for the long-lived phenotype of ksg1 mutation is not yet known. Genetic analysis showed that deletion of pck2 suppressed the long-lived phenotype of ksg1 mutant, suggesting that Pck2 might be involved in the lifespan extension caused by ksg1 mutation.

中文翻译：

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鉴定裂殖酵母中显示长寿命表型的 ksg1 突变

裂殖酵母是研究寿命的良好模式生物。为了阐明机制，我们筛选了长寿突变体。我们在ksg 1 ⁺基因中发现了一个无义突变，该基因编码哺乳动物 PDK1（磷酸肌醇依赖性蛋白激酶）的直向同源物。该突变发生在 Ksg1 的 PH 结构域，导致膜定位和蛋白质稳定性缺陷。对ksg1突变体的分析表明，Ksg1 蛋白的数量和/或活性降低是寿命延长的原因。Ksg1 对生长至关重要，已知可磷酸化多种底物，但导致ksg1突变的长期表型的底物尚不清楚。遗传分析表明，删除pck2抑制了ksg1突变体的长寿表型，表明 Pck2 可能参与了ksg1突变引起的寿命延长。