How Does SIRT1 Affect Metabolism, Senescence and Cancer?

Nat Rev Cancer. 2009 Feb;9(2):123-8. doi: 10.1038/nrc2562. Epub 2008 Dec 29.

Abstract

SIRT1 is a multifaceted, NAD(+)-dependent protein deacetylase that is involved in a wide variety of cellular processes from cancer to ageing. The function of SIRT1 in cancer is complex: SIRT1 has been shown to have oncogenic properties by downregulating p53 activity, but recent studies indicate that SIRT1 acts as a tumour suppressor in a mutated p53 background, raising intriguing questions regarding its mechanism of action. Here we discuss the current understanding of how SIRT1 functions in light of recent discoveries and propose that the net outcome of the seemingly opposite oncogenic and tumour-suppressive effects of SIRT1 depends on the status of p53.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Aging*
  • Animals
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / enzymology*
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Protein Binding
  • Signal Transduction
  • Sirtuin 1
  • Sirtuins / genetics
  • Sirtuins / metabolism*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Tumor Suppressor Protein p53
  • SIRT1 protein, human
  • Sirtuin 1
  • Sirtuins