SKN-1 Is a Negative Regulator of DAF-16 and Somatic Stress Resistance in Caenorhabditis elegans
SKN-1 Is a Negative Regulator of DAF-16 and Somatic Stress Resistance in Caenorhabditis elegans
复制标题
SKN-1 是秀丽隐杆线虫 DAF-16 和躯体应激抵抗力的负调节因子
DOI：
10.1534/g3.120.401203
复制
发表时间：
2020-05-01
影响因子：
2.6
通讯作者：
Pang, Shanshan
中科院分区：
文献类型：
--
作者：
Deng, Jianhui;Dai, Yuxi;Pang, Shanshan
转录因子SKN-1、C.哺乳动物Nrf蛋白的直向同源物，是众所周知的长寿因子，并且在几种长寿模型中观察到其激活。SKN-1还在异生物质和氧化应激反应中发挥重要作用。在这里，我们报告的有害功能SKN-1在体细胞应激抗性，可能会损害寿命。组成性SKN-1激活损害动物对几种应激的抵抗力，包括热、ER应激和线粒体应激，这是由另一种长寿的主要调节因子β-16的抑制引起的。SKN-1的激活消除了E16的核输入，并下调E16靶基因在胁迫条件下，而SKN-1的抑制促进E16靶基因的表达，即使在长寿命的突变体。此外，SKN-1激活诱导卵黄蛋白原蛋白的表达，这是SKN-1介导的抑制β-16和胁迫抗性所必需的。总之，这些发现确定了SKN-1激活在动物健康中的有害作用，更重要的是，激发了对SKN-1在衰老调节中复杂作用的重新思考。
The transcription factor SKN-1, the C. elegans ortholog of mammalian Nrf protein, is a well-known longevity factor, and its activation is observed in several long-lived models. SKN-1 also plays essential roles in xenobiotic and oxidative stress responses. Here, we report deleterious functions of SKN-1 in somatic stress resistance that may impair lifespan. Constitutive SKN-1 activation impairs animal resistance to several stresses, including heat, ER stress and mitochondrial stress, which result from the suppression of DAF-16, another master regulator of longevity. SKN-1 activation abrogates DAF-16 nuclear import and downregulates DAF-16 target genes under stress conditions, while SKN-1 inhibition promotes the expression of DAF-16 targets, even in long-lived mutants. Further, SKN-1 activation induces the expression of vitellogenin proteins, which are required for SKN-1-mediated suppression of DAF-16 and stress resistance. Together, these findings identify detrimental roles for SKN-1 activation in animal health, and more importantly, inspire the rethinking of the complex roles for SKN-1 in aging regulation.