Androgen receptor coregulator ARA267-alpha interacts with death receptor-6 revealed by the yeast two-hybrid.

Institute of Urology, First Hospital of Peking University, Beijing 100034, China.
Science in China Series C Life Sciences (Impact Factor: 1.61). 11/2004; 47(5):442-8. DOI: 10.1360/03yc0214
Source: PubMed


ARA267-alpha is a newly identified androgen receptor coactivator. In order to further elucidate its precise role in cells, using the ARA267-alpha fragment containing four PHD and one SET conserved domains as bait we revealed an ARA267-alpha-PHD-SET-interacting protein, death receptor-6 (DR6), in the yeast two-hybrid screening. DR6 is the member of TNF receptor family and has a death domain in its intracellular cytoplasmic portion (DR6cp) to mediate the cell apoptosis. The interaction between ARA267-alpha-PHD-SET and DR6cp was confirmed in vitro and in vivo. Our finding implied that androgen signaling pathway might cross talk with apoptosis signaling pathway through the interaction between ARA267-alpha and DR6.

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    ABSTRACT: Prostate cancer is the second most common malignancy among males after lung cancer. The growth of prostate cancer cells depends on the presence of androgens, a group of steroid hormones that include testosterone and its more active metabolite dihydrotestoste-rone. Most prostate cancers are androgen-dependent and respond to the antiandrogens or androgen-deprivation therapy. However, the progression to an androgen-independent stage occurs frequently. Possible mechanisms that could be involved in the development of hormone resistant prostate cancer causes including androgen receptor (AR) mutations, AR amplification/over expression, interaction between AR and other growth factors, and enhanced signaling in a ligand-independent manner are discussed.
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