Journal Article

Inhibition of SIRT1 deacetylase suppresses estrogen receptor signaling

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

in Carcinogenesis

Volume 31, issue 3, pages 382-387
Published in print March 2010 | ISSN: 0143-3334
Published online December 2009 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgp308
Inhibition of SIRT1 deacetylase suppresses estrogen receptor signaling

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Estrogen receptor α (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 ERα signaling. Here, we report that human SIRT1, a class III HDAC, regulates ERα expression. Inhibition of SIRT1 activity by sirtinol suppresses ERα expression through disruption of basal transcriptional complexes at the ERα promoter. This effect leads to inhibition of estrogen-responsive gene expression. Our in vitro observations were further extended that SIRT1 knockout reduces ERα protein in mouse mammary gland. Finally, ERα-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 ERα-mediated signaling pathways.

Journal Article.  3966 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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