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

A c-Myc-SIRT1 feedback loop regulates cell growth and transformation.

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1
Division of Oncology Research, Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA.

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.

PMID:
19364925
PMCID:
PMC2700370
DOI:
10.1083/jcb.200809167
[Indexed for MEDLINE]
Free PMC Article
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