Inhibition of SIRT1 deacetylase suppresses estrogen receptor signaling

Yuan Yao, Hongzhe Li, Yansong Gu, Nancy E. Davidson, Qun Zhou

Research output: Contribution to journalArticle

Abstract

Estrogen receptor a (ERα) mediates estrogen-dependent gene transcription, which plays a critical role in mammary gland development, reproduction and homeostasis. Histone acetyltransferases and class I and class II histone deacetylases (HDACs) cause posttranscriptional modification of histone proteins that participate in ERa signaling. Here, we report that human SIRT1, a class III HDAC, regulates ERa expression. Inhibition of SIRT1 activity by sirtinol suppresses ERa expression through disruption of basal transcriptional complexes at the ERa promoter. This effect leads to inhibition of estrogen-responsive gene expression. Our in vitro observations were further extended that SIRT1 knockout reduces ERa protein in mouse mammary gland. Finally, ERa-mediated estrogen response genes are also decreased in mouse embryonic fibroblasts derived from SIRT1-knockout mice. These results suggest that inhibition of SIRT1 deacetylase activity by either pharmacological inhibitors or genetic depletion impairs ERa-mediated signaling pathways.

Original languageEnglish (US)
Pages (from-to)382-387
Number of pages6
JournalCarcinogenesis
Volume31
Issue number3
DOIs
StatePublished - Mar 2010
Externally publishedYes

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Estrogen Receptors
Estrogens
Histone Deacetylases
Human Mammary Glands
Histone Code
Histone Acetyltransferases
Knockout Mice
Genes
Reproduction
Homeostasis
Fibroblasts
Pharmacology
Gene Expression
Proteins
Mouse Era protein
sirtinol
In Vitro Techniques

ASJC Scopus subject areas

  • Cancer Research

Cite this

Yao, Y., Li, H., Gu, Y., Davidson, N. E., & Zhou, Q. (2010). Inhibition of SIRT1 deacetylase suppresses estrogen receptor signaling. Carcinogenesis, 31(3), 382-387. https://doi.org/10.1093/carcin/bgp308

Inhibition of SIRT1 deacetylase suppresses estrogen receptor signaling. / Yao, Yuan; Li, Hongzhe; Gu, Yansong; Davidson, Nancy E.; Zhou, Qun.

In: Carcinogenesis, Vol. 31, No. 3, 03.2010, p. 382-387.

Research output: Contribution to journalArticle

Yao, Y, Li, H, Gu, Y, Davidson, NE & Zhou, Q 2010, 'Inhibition of SIRT1 deacetylase suppresses estrogen receptor signaling', Carcinogenesis, vol. 31, no. 3, pp. 382-387. https://doi.org/10.1093/carcin/bgp308
Yao, Yuan ; Li, Hongzhe ; Gu, Yansong ; Davidson, Nancy E. ; Zhou, Qun. / Inhibition of SIRT1 deacetylase suppresses estrogen receptor signaling. In: Carcinogenesis. 2010 ; Vol. 31, No. 3. pp. 382-387.
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