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VRK-1 extends life span by activation of AMPK via phosphorylation.
Science Advances ( IF 11.7 ) Pub Date : 2020-07-01 , DOI: 10.1126/sciadv.aaw7824
Sangsoon Park 1 , Murat Artan 1 , Seung Hyun Han 2 , Hae-Eun H Park 3 , Yoonji Jung 3 , Ara B Hwang 1 , Won Sik Shin 2 , Kyong-Tai Kim 1, 2 , Seung-Jae V Lee 3
Affiliation  

Vaccinia virus–related kinase (VRK) is an evolutionarily conserved nuclear protein kinase. VRK-1, the single Caenorhabditis elegans VRK ortholog, functions in cell division and germline proliferation. However, the role of VRK-1 in postmitotic cells and adult life span remains unknown. Here, we show that VRK-1 increases organismal longevity by activating the cellular energy sensor, AMP-activated protein kinase (AMPK), via direct phosphorylation. We found that overexpression of vrk-1 in the soma of adult C. elegans increased life span and, conversely, inhibition of vrk-1 decreased life span. In addition, vrk-1 was required for longevity conferred by mutations that inhibit C. elegans mitochondrial respiration, which requires AMPK. VRK-1 directly phosphorylated and up-regulated AMPK in both C. elegans and cultured human cells. Thus, our data show that the somatic nuclear kinase, VRK-1, promotes longevity through AMPK activation, and this function appears to be conserved between C. elegans and humans.



中文翻译:

VRK-1 通过磷酸化激活 AMPK 来延长寿命。

牛痘病毒相关激酶 (VRK) 是一种进化上保守的核蛋白激酶。VRK-1,单一秀丽隐杆线虫VRK 直系同源物,在细胞分裂和生殖系增殖中起作用。然而,VRK-1 在有丝分裂后细胞和成年寿命中的作用仍然未知。在这里,我们表明 VRK-1 通过直接磷酸化激活细胞能量传感器 AMP 活化蛋白激酶 (AMPK) 来延长机体寿命。我们发现在成年秀丽隐杆线虫的胞体中过表达vrk-1会延长寿命,相反,抑制vrk-1会缩短寿命。此外,vrk-1是由抑制秀丽隐杆线虫的突变赋予的长寿所必需的线粒体呼吸,需要 AMPK。VRK-1 在秀丽隐杆线虫和培养的人类细胞中直接磷酸化和上调 AMPK 。因此,我们的数据表明,体细胞核激酶 VRK-1 通过激活 AMPK 来延长寿命,并且这种功能在秀丽隐杆线虫和人类之间似乎是保守的。

更新日期:2020-07-01
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