Anne Brunet, Department of Genetics, Stanford
Anne Brunet is well known for her work on "longevity genes," FOXOs and Sirtuins. She was principal investigator of a 2004 study showing that interaction between SIRT1 and FOXO3a shifted cellular actions away from apoptosis, increasing cell resistance.
Stress-Dependent Regulation of FOXO Transcription Factors by the SIRT1 Deacetylase
Science. 2004 Feb 19
Brunet A et al
The Sir2 deacetylase modulates organismal lifespan in various species. However, the molecular mechanisms by which Sir2 increases longevity are largely unknown. We show that in mammalian cells, the Sir2 homologue SIRT1 appears to control the cellular response to stress by regulating FOXO transcription factors, a family of proteins that function as sensors of the insulin signaling pathway and as regulators of organismal longevity. SIRT1 and the FOXO transcription factor FOXO3 formed a complex in cells in response to oxidative stress and SIRT1 deacetylated FOXO3 in vitro and within cells. SIRT1 had a dual effect on FOXO3 function: SIRT1 increased FOXO3's ability to induce cell cycle arrest and resistance to oxidative stress but inhibited FOXO3's ability to induce cell death. Thus, one way in which members of the Sir2 family of proteins may increase organismal longevity is by tipping FOXO-dependent responses away from apoptosis and toward stress resistance.