Chapter

Histone Deacetylases: the Biology and Clinical Implication

Volume 206 of the series Handbook of Experimental Pharmacology pp 189-224

Date:

Characterization of Nuclear Sirtuins: Molecular Mechanisms and Physiological Relevance

  • Debra ToiberAffiliated withThe Massachusetts General Hospital Cancer Center, Harvard Medical School
  • , Carlos SebastianAffiliated withThe Massachusetts General Hospital Cancer Center, Harvard Medical School
  • , Raul MostoslavskyAffiliated withThe Massachusetts General Hospital Cancer Center, Harvard Medical School Email author 

* Final gross prices may vary according to local VAT.

Get Access

Abstract

Sirtuins are protein deacetylases/mono-ADP-ribosyltransferases found in organisms ranging from bacteria to humans. This group of enzymes relies on nicotinamide adenine dinucleotide (NAD+) as a cofactor linking their activity to the cellular metabolic status. Originally found in yeast, Sir2 was discovered as a silencing factor and has been shown to mediate the effects of calorie restriction on lifespan extension. In mammals seven homologs (SIRT1−7) exist which evolved to have specific biological outcomes depending on the particular cellular context, their interacting proteins, and the genomic loci to where they are actively targeted. Sirtuins biological roles are highlighted in the early lethal phenotypes observed in the deficient murine models. In this chapter, we summarize current concepts on non-metabolic functions for sirtuins, depicting this broad family from yeast to mammals.

Keywords

Angiogenesis α-synuclein Caenorhabditis elegans Caloric restriction Cellular senescence Chronological life span Drosophila Fragile X syndrome Glucose metabolism HML and HMR Hst proteins Hypoxia Nucleotide Parkinson’s disease Senescence Sir2