Sirtuin-mediated deacetylation pathway stabilizes Werner syndrome protein.
Caloric restriction (CR) is known to promote longevity in various species. Sirtuin-mediated deacetylation has been shown to be related to the promotion of longevity in some species. Here, we show that CR of rats led to an increase in the level of Werner syndrome protein (WRN), a recognized DNA repair protein. In addition, CR simultaneously increased the level of SIRT1, a mammalian sirtuin. In HEK293T cells, sirtuin inhibitors decreased the WRN level, and this effect was suppressed by proteasomal inhibitors. Furthermore, we found a decrease in the WRN level in Sirt1-deficient mice. These results indicate that sirtuin-mediated deacetylation stabilizes WRN. STRUCTURED SUMMARY:
Kahyo
Tomoaki
T
Molecular Gerontology Research Group, Mitsubishi Kagaku Institute of Life Sciences, Minamiooya, Machida, Tokyo, Japan.
Mostoslavsky
Raul
R
Goto
Makoto
M
Setou
Mitsutoshi
M
D000107:Acetylation; D000818:Animals; D031204:Caloric Restriction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004795:Enzyme Stability; D005090:Exodeoxyribonucleases / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000201:enzymology; D051379:Mice; D008817:Mice, Mutant Strains; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D051381:Rats; D053484:RecQ Helicases / Q000378:metabolism*; D056564:Sirtuin 1; D037761:Sirtuins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000071657:Werner Syndrome Helicase
D004791:Enzyme Inhibitors; D005090:Exodeoxyribonucleases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D037761:Sirtuins; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase