title: DNA homologous recombination factor SFR1 physically and functionally interacts with estrogen receptor alpha.
abstract: 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.
authors.affiliation: Department of Cancer Biology, College of Medicine, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Feng
authors.forename: David
authors.initials: D
authors.lastname: Singleton
authors.forename: Chun
authors.initials: C
authors.lastname: Guo
authors.forename: Amanda
authors.initials: A
authors.lastname: Gardner
authors.forename: Suresh
authors.initials: S
authors.lastname: Pakala
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kumar
authors.forename: Elwood
authors.initials: E
authors.lastname: Jensen
authors.forename: Jinsong
authors.initials: J
authors.lastname: Zhang
authors.forename: Sohaib
authors.initials: S
authors.lastname: Khan
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D059765:Homologous Recombination / Q000502:physiology; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques
chemical_list: D002352:Carrier Proteins; D047628:Estrogen Receptor alpha; D009687:Nuclear Proteins; D012333:RNA, Messenger; C558174:SFR1 protein, human; D014157:Transcription Factors