Elucidation of the roles of protein deacetylase SIRT1 in health and diseases

Abstract

Elucidation of aging is one of the most important goals of science in the post-genomic era. NAD+-dependent protein deacetylase was firstly identified as yeast silent information regulator 2 (Sir2), overexpression of which has the ability to extend the life span in yeast, Drosophila and aenorhabditis elegans. SIRT1 is a mammalian homologue of yeast Sir2. We are studying SIRT1 and investigating roles of SIRT1 in health and diseases. SIRT1 has a variety of substrate proteins such as transcription factor FOXOs, transcription coactivator PGC1 α , and proteins involved in the autophagy process. found that SIRT1 activation reduces cellular oxidative stress and improves skeletal muscle activities and cardiac function in muscular dystrophy model animals and also dystrophy patients. SIRT1 also involves in cellular migration. We found that melanoma expresses SIRT1 in lamellipodia, which is necessary for migration of melanoma cells. We found that the inhibition of SIRT1 prevents melanoma migration in vitro and in vivo. Inhibition of SIRT1 by an inhibitor significantly decreased metastasis in mice transplanted with melanoma cells.