SIRT1 is critical regulator of FOXO-mediated transcription in response to oxidative stress

• DOI: 10.3892/ijmm.16.2.237
• Publication Date: 2014-03-10T07:37:34Z
• Authors: Yosuke Kobayashi; Yoko Furukawa-Hibi; Chen Chen; Yoshiyuki Horio; Kenichi Isobe; Kyoji Ikeda; Noboru Motoyama
• Keywords: Sirtuin 1; Forkhead Transcription Factors; Gadd45

Forkhead transcription factor, DAF-16, regulates genes that contribute both to longevity and resistance various stresses in C. elegans. We others have reported members of the FOXO, mammalian homologs also regulate related stress resistance, such as GADD45. The NAD-dependent protein deacetylase, SIR2, is required for life span extension yeast induced by caloric restriction, which increases a wide variety other organisms, including mammals. Sir2.1, homolog extends acting DAF-16 signaling pathway demonstrate SIRT1 (Sir2α) physiologically interacts with FOXO. Acetylation FOXO4, transcriptional coactivator p300, counteracted activation FOXO4 p300. In contrast, was found bind catalyze its deacetylation an manner, thereby increase transactivation activity. activity suppressed or enhanced inhibitor, nicotinamide, activator, resveratrol, respectively. response oxidative stress, FOXO accumulates within nucleus induces GADD45 expression. FOXO-mediated induction markedly impaired cell, depleted expression RNA-interference. These results indicate plays pivotal role function via may cellular longevity.