SIRT1 and p53, effect on cancer, senescence and beyond

Biochim Biophys Acta. 2010 Aug;1804(8):1684-9. doi: 10.1016/j.bbapap.2010.05.002. Epub 2010 May 13.

Abstract

NAD(+)-dependent Class III histone deacetylase SIRT1 is a multiple function protein critically involved in stress responses, cellular metabolism and aging through deacetylating a variety of substrates including p53, forkhead-box transcription factors, PGC-1alpha, NF-kappaB, Ku70 and histones. The first discovered non-histone target of SIRT1, p53, is suggested to play a central role in SIRT1-mediated functions in tumorigenesis and senescence. SIRT1 was originally considered to be a potential tumor promoter since it negatively regulates the tumor suppressor p53 and other tumor suppressors. There is new evidence that SIRT1 acts as a tumor suppressor based on its role in negatively regulating beta-catenin and survivin. This review provides an overview of current knowledge of SIRT1-p53 signaling and controversies regarding the functions of SIRT1 in tumorigenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging / metabolism*
  • Animals
  • Apoptosis
  • Cellular Senescence
  • Humans
  • Mice
  • Models, Biological
  • Neoplasms / etiology
  • Neoplasms / metabolism*
  • Nerve Degeneration / etiology
  • Nerve Degeneration / metabolism
  • Oxidative Stress
  • Signal Transduction
  • Sirtuin 1 / metabolism*
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Tumor Suppressor Protein p53
  • Sirtuin 1