Cynthia Wolberger, Ph.D.
Substrates of the Sir2 Family of Enzymes
Sirtuins, also known as Sir2 enzymes, are NAD+-dependent lysine deacetylases that play key roles in many biological processes including transcriptional silencing, inflammation, fat mobilization and aging. Despite the central role sirtuins play in many pathways, relatively few biological substrates are known. We are using the resources of the Technology Center for Networks and Pathways of Lysine Modification to screen for in vivo targets of sirtuins. We have devised a novel assay that uses yeast protein microarrays to identify proteins that are deacetylated by each of the five yeast sirtuins, followed by mass spectrometry analysis to pinpoint the deacetylated lysines. These experiments will lay the groundwork for eventual studies of the targets of the human Sir2 enzymes.