Negative regulation of ER¦Á by a novel protein CAC1 through association with histone demethylase LSD1

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• 作者：JuHyun Kim^a ; ¹ ; Ui-Hyun Park^b ; ¹ ; MinO Moon^a ; Soo-Jong Um^b ; ^{umsj@sejong.ac.kr} ; Eun-Joo Kim^a ; ^{nbrejk@dankook.ac.kr}
• 关键词：CAC1 ; CDK2-assocaited cullin ; ER¦Á ; estrogen receptor alpha ; LSD1 ; lysine specific demethylase 1 ; GST ; glutathione S-transferase ; ¦Â-gal ; ¦Â-galactosidase ; GFP ; green fluorescent protein ; ERE ; ER-responsive element
• 刊名：FEBS Letters
• 出版年：2013
• 出版时间：4 January, 2013
• 年：2013
• 卷：587
• 期：1
• 页码：17-22
• 全文大小：602 K

文摘

ER¦Á, a critical transcriptional factor for breast cancer proliferation, is regulated by a complex binding repertoire that includes coactivators and corepressors. Here, we identified a novel class of ER¦Á coregulator called CAC1. The CoRNR box of CAC1 was required for the binding to and inactivation of ER¦Á. CAC1 also associated with histone demethylase LSD1 and suppressed LSD1-enhanced ER¦Á activity. CAC1 impaired recruitment of ER¦Á and LSD1 to the ER¦Á-responsive promoter, leading to greater H3K9me3 accumulation. This effect was reversed by CAC1 depletion. Finally, CAC1 increased paclitaxel-induced cell death in ER¦Á-positive MCF7 cells, which are paclitaxel-resistant. Overall, our study provides the first evidence that CAC1, associated with LSD1, functions as an ER¦Á corepressor, implicating a potential antitumor target in ER¦Á-positive breast cancer.

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