FBI-1 functions as a novel AR co-repressor in prostate cancer cells

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.

Long interspersed nucleotide acid element-1 ORF-1 protein promotes proliferation and invasion of human colorectal cancer LoVo cells through enhancing ETS-1 activity

“…The following reagents were used: Lipofectamine (Invitrogen Corp., USA), Dulbecco's modified Eagle's medium (DMEM; Hyclone Company, USA), fetal bovine serum (FBS; Gibco, USA), and neomycin G418 (Sigma Company, USA). The following antibodies were used: rabbit anti-LINE-1 ORF-1p polyclonal antibodies (Cui et al, 2011), anti-GADPH polyclonal rabbit antibody (Sigma), horseradish peroxidase (HRP)-conjugated goat-anti-rabbit IgG (Santa Cruz, USA), rabbit anti-ETS-1 monoclonal antibody (Sigma), rabbit anti-MMP-1, anti-MMP-9 polyclonal antibody, and anti-Survivin monoclonal antibodies (Santa Cruz). The following cells were used: colorectal cancer cell lines LoVo, HR8348, and HT29, the HCC cell line HepG2, the breast cancer cell line MCF-7, and the lung cancer cell line A549 (Chinese Academy of Medical Sciences, China).…”

Flightless I Homolog Represses Prostate Cancer Progression through Targeting Androgen Receptor Signaling

“…ARA67/PAT1 binds to AR multiple domains and suppresses AR transactivation by interrupting nuclear localization of AR (42). FBI-1 has been reported to suppress the AR transcription activity, which is dependent on the binding to AR (44). Unfortunately the role of AR corepressors during prostate cancer progression was unclear.…”

“…In the presence of AR agonist, NCoR and SMRT can be recruited to the PSA promoter and repress the PSA expression (46). Corepressors of AR that trigger chromatin condensation and/or chromatin modifications typically recruit HDACs to the AR complex (44). The well-characterized corepressors NCoR and SMRT could directly interact with multiple HDACs and recruit them to AR (44,47).…”

Role of LRF/Pokemon in lineage fate decisions

“…Recently, however, the inventory of LRF/Pokemon interactors has been expanded to include other transcription factors such as tumor protein p53 (TP53), androgen receptor, specificity protein 1, BCL6, sex determining region Y-box 9 (SOX9), and growth factor independent 1, thereby suggesting an indirect transcriptional repressive activity of LRF on specific subclasses of genes ( Figure 1B). [10][11][12][13][14][15][16][17][18] These findings in turn highlight LRF as a key node for the transcriptional regulation of fundamental pathways involved in cell cycle control, apoptosis, and cell fate decision.…”

“…Finally, the poorly conserved hinge region between the POZ and ZF domains, as well as the C terminus at the end of the ZFs domains, are often the targets of posttranslational modifications responsible for the regulation of protein function ( Figure 1A). [10][11][12][13][14][15][16][17][18] Multiple POK proteins, LRF included, have been shown to act as transcriptional repressors by directly binding specific consensus sequences on DNA and interacting with corepressors such as NCoR, SMRT, and Sin3a via the POZ domain at the N terminus. 19,20 For its part, LRF preferentially binds to the GC-rich sequence [(G/A)(C/A)GACCCC], as has been revealed by cyclic amplification and selection of target analysis, 21 gelshift assay, 22 and chromatin immunoprecipitation sequencing.…”