SIRT1: Importance of O-GlcNAc and phosphorylation interplay in aging and diabetes

Sirtuins are conserved protein deacetylases or adp ribosyltransferases acting on broad range of cellular proteins. the target proteins are present in the nucleus,cytoplasm,and mitochondria and are posttranslationally modified by acetylation via silent mating type information regulation 2 homolog 1 (sirt1). among the rest of the sirtuins,sirt1 is most studied and is involved in the process of aging and controls the extent of life span. different post-translational modifications (ptms) such as phosphorylation and glycosylation control the function of sirt1. in the present study,the role of these modifications and their interplay,involving the regulation of the transcriptional activity of sirt1,has been examined in silico. the current study suggests that transcriptional activity of sirt1 is increased by phosphorylation,while glycosylation decrease it. during aging and diabetes,addition of o-glcnac attenuates the activity of sirt1 on the function of related proteins. these ptms play an important role in regulation of various activities of sirt1 which range from homeostasis,survival and aging. copyright 2013 zoological society of pakistan.