VRK-1 extends life span by activation of AMPK via phosphorylation

article VRK-1 extends life span by activation of AMPK via phosphorylation published yes Sangsoon Park author Murat Artan author C407B586-6052-11E9-B3AE-7006E66974250000-0001-8945-6992 Seung Hyun Han author Hae-Eun H. Park author Yoonji Jung author Ara B. Hwang author Won Sik Shin author Kyong-Tai Kim author Seung-Jae V. Lee author MaDe department 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. https://research-explorer.ista.ac.at/download/15057/15058/2020_ScienceAdvances_Park.pdf application/pdfno American Association for the Advancement of Science2020 eng Science Advances 2375-254810.1126/sciadv.aaw7824 627 Park, Sangsoon, et al. “VRK-1 Extends Life Span by Activation of AMPK via Phosphorylation.” Science Advances, vol. 6, no. 27, aaw7824, American Association for the Advancement of Science, 2020, doi:<a href="https://doi.org/10.1126/sciadv.aaw7824">10.1126/sciadv.aaw7824</a>. Park, S., Artan, M., Han, S. H., Park, H.-E. H., Jung, Y., Hwang, A. B., … Lee, S.-J. V. (2020). VRK-1 extends life span by activation of AMPK via phosphorylation. Science Advances. American Association for the Advancement of Science. <a href="https://doi.org/10.1126/sciadv.aaw7824">https://doi.org/10.1126/sciadv.aaw7824</a> Park S, Artan M, Han SH, et al. VRK-1 extends life span by activation of AMPK via phosphorylation. Science Advances. 2020;6(27). doi:<a href="https://doi.org/10.1126/sciadv.aaw7824">10.1126/sciadv.aaw7824</a> S. Park, M. Artan, S.H. Han, H.-E.H. Park, Y. Jung, A.B. Hwang, W.S. Shin, K.-T. Kim, S.-J.V. Lee, Science Advances 6 (2020). Park, Sangsoon, Murat Artan, Seung Hyun Han, Hae-Eun H. Park, Yoonji Jung, Ara B. Hwang, Won Sik Shin, Kyong-Tai Kim, and Seung-Jae V. Lee. “VRK-1 Extends Life Span by Activation of AMPK via Phosphorylation.” Science Advances. American Association for the Advancement of Science, 2020. <a href="https://doi.org/10.1126/sciadv.aaw7824">https://doi.org/10.1126/sciadv.aaw7824</a>. Park S, Artan M, Han SH, Park H-EH, Jung Y, Hwang AB, Shin WS, Kim K-T, Lee S-JV. 2020. VRK-1 extends life span by activation of AMPK via phosphorylation. Science Advances. 6(27), aaw7824. S. Park et al., “VRK-1 extends life span by activation of AMPK via phosphorylation,” Science Advances, vol. 6, no. 27. American Association for the Advancement of Science, 2020. 150572024-03-04T09:41:57Z2024-03-04T09:52:09Z