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.
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Acknowledgments
We thank Dr. Glass for kindly providing FLAG-NCoR and FLAG-SMRT. This work was supported by the grant from the National Natural Science Foundation of China (No. 30772001 and No. 30671927) and Beijing Municipal Natural Science Foundation (No. 7102126).
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J. Cui, Y. Yang and C. Zhang were contributed equally to this work.
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Cui, J., Yang, Y., Zhang, C. et al. FBI-1 functions as a novel AR co-repressor in prostate cancer cells. Cell. Mol. Life Sci. 68, 1091–1103 (2011). https://doi.org/10.1007/s00018-010-0511-7
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DOI: https://doi.org/10.1007/s00018-010-0511-7