Park Sangsoon, Artan Murat, Han Seung Hyun, Park Hae-Eun H, Jung Yoonji, Hwang Ara B, Shin Won Sik, Kim Kyong-Tai, Lee Seung-Jae V
Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea.
Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea.
Sci Adv. 2020 Jul 1;6(27). doi: 10.1126/sciadv.aaw7824. Print 2020 Jul.
Vaccinia virus-related kinase (VRK) is an evolutionarily conserved nuclear protein kinase. VRK-1, the single 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 in the soma of adult increased life span and, conversely, inhibition of decreased life span. In addition, was required for longevity conferred by mutations that inhibit mitochondrial respiration, which requires AMPK. VRK-1 directly phosphorylated and up-regulated AMPK in both 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 and humans.
痘苗病毒相关激酶（VRK）是一种在进化上保守的核蛋白激酶。VRK-1是VRK的唯一直系同源物，在细胞分裂和生殖系增殖中发挥作用。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激活的蛋白激酶（AMPK）来延长生物体的寿命。我们发现，在成年线虫的体细胞中过表达VRK-1可延长寿命，相反，抑制VRK-1则会缩短寿命。此外，抑制线粒体呼吸的突变所赋予的长寿需要VRK-1，而线粒体呼吸需要AMPK。VRK-1在秀丽隐杆线虫和培养的人类细胞中均直接磷酸化并上调AMPK。因此，我们的数据表明，体细胞核激酶VRK-1通过激活AMPK来促进长寿，并且这种功能在秀丽隐杆线虫和人类之间似乎是保守的。
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