The ups and downs of SIRT1

Trends Biochem Sci. 2008 Nov;33(11):517-25. doi: 10.1016/j.tibs.2008.08.001. Epub 2008 Sep 18.


Reversible acetylation has emerged as a key post-translational modification of proteins. Although the number of acetylated proteins is rapidly growing, the ways in which protein acetyltransferases and deacetylases connect with extracellular stimuli remain unclear. Recently, a regulatory network has emerged that controls the expression and activity of SIRT1, a mammalian class-III protein deacetylase. SIRT1 is an important regulator of metabolism, senescence, cancer and, possibly, longevity and is connected with crucial stress-responsive signal-transduction pathways. These connections provide important clues about how protein acetylation and deacetylation mediate cellular adaptations to extrinsic stress.

Publication types

  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / physiology
  • Animals
  • Caloric Restriction
  • Down-Regulation
  • Gene Expression Regulation
  • Gene Products, tat / physiology
  • Humans
  • Mice
  • Nuclear Proteins / physiology
  • PC12 Cells
  • Rats
  • SUMO-1 Protein / physiology
  • Signal Transduction
  • Sirtuin 1
  • Sirtuins / biosynthesis
  • Sirtuins / physiology*
  • Stress, Physiological / physiology
  • Transcription Factors / physiology
  • Transcription, Genetic / drug effects
  • Up-Regulation


  • Adaptor Proteins, Signal Transducing
  • CCAR2 protein, human
  • Gene Products, tat
  • Nuclear Proteins
  • RPS19BP1 protein, human
  • SUMO-1 Protein
  • Transcription Factors
  • SIRT1 protein, human
  • Sirtuin 1
  • Sirtuins