Organic Chemistry Seminar
Sirtuins are known as nicotinamide adenine dinucleotide (NAD)-dependent deacetylases. They regulate aging, transcription, and metabolism, and are considered important targets for treating several human diseases. There are seven sirtuins in humans, SIRT1-7. Four of them (SIRT4-7) have very weak deacetylase activity, which have caused many confusions and debates in the biological community. My laboratory has recently discovered several novel enzymatic activities, such as desuccinylation and defatty-acylation, for several sirtuins with no robust deacetylase activity. This have led to the identification of previously unknown protein post-translational modifications (PTMs) and revealed new regulatory mechanisms of cell signaling pathways. Furthermore, these findings have enabled us to develop compounds that can inhibit particular sirtuins selectively. Some of the selective sirtuins inhibitors can kill cancer cells in cell culture and inhibit tumor formation in mouse models at least partly via the regulation of c-Myc and K-Ras. The roles of sirtuins and the new PTMs in cancer are being elucidated.