FBI-1 functions as a novel AR co-repressor in prostate cancer cells.
The pro-oncogene FBI-1, encoded by Zbtb7a, is a transcriptional repressor that belongs to the POK (POZ/BTB and Krueppel) protein family. In this study, we investigated a potential interaction between androgen receptor (AR) signaling and FBI-1 and demonstrated that overexpression of FBI-1 inhibited ligand-dependent AR activation. A protein-protein interaction was identified ... between FBI-1 and AR in a ligand-dependent manner. Furthermore, FBI-1, AR and SMRT formed a ternary complex and FBI-1 enhanced the recruitment of NCoR and SMRT to endogenous PSA upstream sequences. Our data also indicated that the FBI-1-mediated inhibition of AR transcriptional activity is partially dependent on HDAC. Interestingly, FBI-1 plays distinct roles in regulating LNCaP (androgen-dependent) and PC-3 cell (androgen-independent) proliferation.
Mesh Terms:
Cell Line, Tumor, Chromatin Immunoprecipitation, DNA Primers, DNA-Binding Proteins, Histone Deacetylases, Humans, Immunoprecipitation, Luciferases, Male, Multiprotein Complexes, Nuclear Receptor Co-Repressor 2, Plasmids, Prostatic Neoplasms, RNA, Small Interfering, Receptors, Androgen, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Transcription Factors, Transfection
Cell Line, Tumor, Chromatin Immunoprecipitation, DNA Primers, DNA-Binding Proteins, Histone Deacetylases, Humans, Immunoprecipitation, Luciferases, Male, Multiprotein Complexes, Nuclear Receptor Co-Repressor 2, Plasmids, Prostatic Neoplasms, RNA, Small Interfering, Receptors, Androgen, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Transcription Factors, Transfection
Cell. Mol. Life Sci.
Date: Mar. 01, 2011
PubMed ID: 20812024
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