Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-31249
Metzger, E; Müller, J M; Ferrari, S; Buettner, R; Schüle, R (2003). A novel inducible transactivation domain in the androgen receptor: implications for PRK in prostate cancer. EMBO Journal, 22(2):270-280.
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In addition to the classical activation by ligands, nuclear receptor activity is also regulated by ligand-independent signalling. Here, we unravel a novel signal transduction pathway that links the RhoA effector protein kinase C-related kinase PRK1 to the transcriptional activation of the androgen receptor (AR). Stimulation of the PRK signalling cascade results in a ligand-dependent superactivation of AR. We show that AR and PRK1 interact both in vivo and in vitro. The transactivation unit 5 (TAU-5) located in the N-terminus of AR suffices for activation by PRK1. Thus, TAU-5 defines a novel, signal-inducible transactivation domain. Furthermore, PRK1 promotes a functional complex of AR with the co-activator TIF-2. Importantly, PRK signalling also stimulates AR activity in the presence of adrenal androgens, which are still present in prostate tumour patients subjected to testicular androgen ablation therapy. Moreover, PRK1 activates AR even in the presence of the AR antagonist cyproterone acetate that is used in the clinical management of prostate cancer. Since prostate tumours strongly overexpress PRK1, our data support a model in which AR activity is controlled by PRK signalling.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Institute of Molecular Cancer Research|
07 Faculty of Science > Institute of Molecular Cancer Research
|DDC:||570 Life sciences; biology|
|Deposited On:||09 Jul 2010 12:38|
|Last Modified:||26 Dec 2013 08:46|
|Publisher:||Nature Publishing Group|
|Free access at:||Publisher DOI. An embargo period may apply.|
|Citations:||Web of Science®. Times Cited: 54|
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