Regulation of SIRT1 protein levels by nutrient availability.
The mammalian NAD+ dependent deacetylase, SIRT1, was shown to be a key protein in regulating glucose homeostasis, and was implicated in the response to calorie restriction. We show here that levels of SIRT1 increased in response to nutrient deprivation in cultured cells, and in multiple tissues of mice after fasting. The increase in SIRT1 levels was due to stabilization of SIRT1 protein, and not an increase in SIRT1 mRNA. In addition, p53 negatively regulated SIRT1 levels under normal growth conditions and is also required for the elevation of SIRT1 under limited nutrient conditions. These results have important implications on the relationship between sirtuins, nutrient availability and aging.
The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel.
Yariv
Y
Kanfi
Victoria
V
Peshti
Yosi M
YM
Gozlan
Moran
M
Rathaus
Reuven
R
Gil
Haim Y
HY
Cohen
D000818:Animals; D031204:Caloric Restriction; D002460:Cell Line; D016895:Culture Media, Serum-Free; D005215:Fasting; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D056564:Sirtuin 1; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D016895:Culture Media, Serum-Free; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; C447939:SIRT1 protein, human; C470545:Sirt1 protein, mouse; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D037761:Sirtuins