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Updated: Aug 10, 2026

Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation
Published on: June 21, 2016
The retinoblastoma protein-associated transcription repressor RBaK interacts with the androgen receptor and enhances
K Hofman1, J V Swinnen, F Claessens
1Laboratory for Experimental Medicine and Endocrinology, Catholic University of Leuven, Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium.
Abstract:
In search of potential androgen receptor coregulators we performed a yeast two-hybrid screening using the androgen receptor ligand-binding domain as bait and a human prostate cDNA library as prey and found that the carboxy-terminal domain of retinoblastoma-associated Krüppel protein (RbaK), a member of the Krüppel zinc finger protein family, interacts in a ligand-dependent way with the ligand-binding domain of the androgen receptor. RBaK was recently identified as a transcriptional regulator that interacts with the retinoblastoma protein and thereby influences E2F regulated transcription. The interaction of RBaK with the androgen receptor was further documented using mammalian two-hybrid experiments, in vitro binding studies and coimmunoprecipitation. Finally, we demonstrated that both RBaK and the retinoblastoma protein coactivate androgen receptor-mediated transcription in cotransfection experiments. In conclusion, our data show that RBaK interacts with the androgen receptor and increases its transcriptional activity. Moreover, the double interaction of RBaK with the retinoblastoma protein and with the androgen receptor provides a novel link between the androgen receptor and the regulation of the cell cycle.
Insights
Retinoblastoma-associated Krüppel protein (RbaK) interacts with the androgen receptor, enhancing its transcriptional activity. This discovery links androgen receptor signaling to cell cycle regulation.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Biology
Background:
- Androgen receptor (AR) signaling is crucial in prostate cancer.
- Identifying AR coregulators is key to understanding AR function.
- Retinoblastoma-associated Krüppel protein (RbaK) is a known transcriptional regulator.
Purpose of the Study:
- To identify novel androgen receptor coregulators.
- To investigate the interaction between RbaK and the androgen receptor.
- To determine the functional consequence of this interaction on AR activity.
Main Methods:
- Yeast two-hybrid screening using AR ligand-binding domain and a human prostate cDNA library.
- Mammalian two-hybrid assays.
- In vitro binding studies and coimmunoprecipitation.
- Cotransfection experiments to assess transcriptional activity.
Main Results:
- Identified RbaK as a novel AR-interacting protein.
- Demonstrated ligand-dependent interaction between RbaK and the AR ligand-binding domain.
- Showed that RbaK and retinoblastoma protein coactivate AR-mediated transcription.
- Confirmed interaction using multiple experimental approaches.
Conclusions:
- RbaK interacts with the androgen receptor and enhances its transcriptional activity.
- This interaction provides a novel link between AR signaling and cell cycle regulation.
- RbaK represents a potential therapeutic target in AR-driven cancers.
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