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

Jian Yuan, Katherine Minter-Dykhouse, Zhenkun Lou

Research output: Contribution to journalArticle

149 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)203-211
Number of pages9
JournalJournal of Cell Biology
Volume185
Issue number2
DOIs
StatePublished - Apr 20 2009

Fingerprint

Caenorhabditis elegans
Growth
Drosophila melanogaster
Mammals
Neoplasms
Yeasts
Proteins

ASJC Scopus subject areas

  • Cell Biology

Cite this

A c-Myc-SIRT1 feedback loop regulates cell growth and transformation. / Yuan, Jian; Minter-Dykhouse, Katherine; Lou, Zhenkun.

In: Journal of Cell Biology, Vol. 185, No. 2, 20.04.2009, p. 203-211.

Research output: Contribution to journalArticle

@article{c905a61f32174e38ac7f6f3fd6085838,
title = "A c-Myc-SIRT1 feedback loop regulates cell growth and transformation",
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.",
author = "Jian Yuan and Katherine Minter-Dykhouse and Zhenkun Lou",
year = "2009",
month = "4",
day = "20",
doi = "10.1083/jcb.200809167",
language = "English (US)",
volume = "185",
pages = "203--211",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "2",

}

TY - JOUR

T1 - A c-Myc-SIRT1 feedback loop regulates cell growth and transformation

AU - Yuan, Jian

AU - Minter-Dykhouse, Katherine

AU - Lou, Zhenkun

PY - 2009/4/20

Y1 - 2009/4/20

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=65349096174&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=65349096174&partnerID=8YFLogxK

U2 - 10.1083/jcb.200809167

DO - 10.1083/jcb.200809167

M3 - Article

C2 - 19364925

AN - SCOPUS:65349096174

VL - 185

SP - 203

EP - 211

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 2

ER -