A c-Myc-SIRT1 Feedback Loop Regulates Cell Growth and Transformation

J Cell Biol. 2009 Apr 20;185(2):203-11. doi: 10.1083/jcb.200809167. Epub 2009 Apr 13.

Abstract

The protein deacetylase SIRT1 has been implicated in a variety of cellular functions, including development, cellular stress responses, and metabolism. Increasing evidence suggests that similar to its counterpart, Sir2, in yeast, Caenorhabditis elegans, and Drosophila melanogaster, SIRT1 may function to regulate life span in mammals. However, SIRT1's role in cancer is unclear. During our investigation of SIRT1, we found that c-Myc binds to the SIRT1 promoter and induces SIRT1 expression. However, SIRT1 interacts with and deacetylates c-Myc, resulting in decreased c-Myc stability. As a consequence, c-Myc's transformational capability is compromised in the presence of SIRT1. Overall, our experiments identify a c-Myc-SIRT1 feedback loop in the regulation of c-Myc activity and cellular transformation, supporting/suggesting a role of SIRT1 in tumor suppression.

Publication types

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

MeSH terms

  • Acetylation
  • Animals
  • Cell Transformation, Neoplastic*
  • Feedback*
  • Gene Expression Regulation*
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Sirtuin 1
  • Sirtuins / genetics
  • Sirtuins / metabolism*
  • Telomerase / genetics
  • Telomerase / metabolism
  • Transfection

Substances

  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • RNA, Small Interfering
  • TERT protein, human
  • Telomerase
  • SIRT1 protein, human
  • Sirtuin 1
  • Sirtuins