DNA Homologous Recombination Factor SFR1 Physically and Functionally Interacts with Estrogen Receptor Alpha

PLoS One

Rakesh Kumar¹  Elwood Jensen¹  Sohaib Khan²  Yuxin Feng²  Chun Guo²  Suresh Pakala²  Amanda Gardner²  Jinsong Zhang²  David Singleton³ 

[1] Department of Biochemistry and Molecular Biology, George Washington University School of Medicine, Washington, DC, United States of America;Department of Cancer Biology, College of Medicine, University of Cincinnati, Cincinnati, Ohio, United States of America;Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America

关键词: Cell proliferation;    Small interfering RNAs;    Luciferase assay;    DNA transcription;    Breast cancer;    DNA-binding proteins;    Transcriptional control;    Two-hybrid screening;   

DOI  :  10.1371/journal.pone.0068075

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Estrogen receptor alpha (ERα), a ligand-dependent transcription factor, mediates the expression of its target genes by interacting with corepressors and coactivators. Since the first cloning of SRC1, more than 280 nuclear receptor cofactors have been identified, which orchestrate target gene transcription. Aberrant activity of ER or its accessory proteins results in a number of diseases including breast cancer. Here we identified SFR1, a protein involved in DNA homologous recombination, as a novel binding partner of ERα. Initially isolated in a yeast two-hybrid screen, the interaction of SFR1 and ERα was confirmed in vivo by immunoprecipitation and mammalian one-hybrid assays. SFR1 co-localized with ERα in the nucleus, potentiated ER’s ligand-dependent and ligand-independent transcriptional activity, and occupied the ER binding sites of its target gene promoters. Knockdown of SFR1 diminished ER’s transcriptional activity. Manipulating SFR1 expression by knockdown and overexpression revealed a role for SFR1 in ER-dependent and -independent cancer cell proliferation. SFR1 differs from SRC1 by the lack of an intrinsic activation function. Taken together, we propose that SFR1 is a novel transcriptional modulator for ERα and a potential target in breast cancer therapy.

【 授权许可】

CC BY