Abstract
The pro-oncogene FBI-1, encoded by Zbtb7a, is a transcriptional repressor that belongs to the POK (POZ/BTB and Krüppel) 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Line, Tumor
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Chromatin Immunoprecipitation
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DNA Primers / genetics
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DNA-Binding Proteins / metabolism*
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Histone Deacetylases / metabolism
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Humans
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Immunoprecipitation
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Luciferases
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Male
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Multiprotein Complexes / metabolism*
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Nuclear Receptor Co-Repressor 2 / metabolism*
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Plasmids / genetics
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Prostatic Neoplasms / metabolism*
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RNA, Small Interfering / genetics
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Receptors, Androgen / metabolism*
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction / physiology*
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Transcription Factors / metabolism*
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Transfection
Substances
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DNA Primers
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DNA-Binding Proteins
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Multiprotein Complexes
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NCOR2 protein, human
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Nuclear Receptor Co-Repressor 2
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RNA, Small Interfering
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Receptors, Androgen
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Transcription Factors
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ZBTB7A protein, human
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Luciferases
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Histone Deacetylases