This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Callewaert, L. Articles by Claessens, F. Search for Related Content PubMed PubMed Citation Articles by Callewaert, L. Articles by Claessens, F.

Interplay between Two Hormone-Independent Activation Domains in the Androgen Receptor

Molecular Endocrinology Laboratory, Faculty of Medicine, Campus Gasthuisberg, University of Leuven, Leuven, Belgium

Requests for reprints: Frank Claessens, Molecular Endocrinology Laboratory, Faculty of Medicine, Campus Gasthuisberg, University of Leuven, Herestraat 49, B-3000 Leuven, Belgium. Phone: 32-16-345770; Fax: 32-16-345995; E-mail: frank.claessens{at}med.kuleuven.ac.be.

The androgen receptor (AR) plays a key role in prostate cancer development, as well as its treatments, even for the hormone-refractory state. Here, we report that an earlier described lysine-to-arginine mutation at position 179 in AR leads to a more potent AR. We show that two activation domains (Tau-1 and Tau-5) are necessary and sufficient for the full activity of AR and the intrinsic activity of the AR-NTD. Two -helices surrounding the Lys¹⁷⁹ define the core of Tau-1, which can act as an autonomous activation function, independent of p160 coactivators. Furthermore, we show that although the recruitment of p160 coactivators is mediated through Tau-5, this event is attenuated by core Tau-1. This better definition of the mechanisms of action of both Tau-1 and Tau-5 is instrumental for the design of alternative therapeutic strategies against prostate cancer. (Cancer Res 2006; 66(1): 543-53)

This article has been cited by other articles:

				S. Bai and E. M. Wilson Epidermal Growth Factor-Dependent Phosphorylation and Ubiquitinylation of MAGE-11 Regulates Its Interaction with the Androgen Receptor Mol. Cell. Biol., March 15, 2008; 28(6): 1947 - 1963. [Abstract] [Full Text] [PDF]

				S. M. Dehm and D. J. Tindall Androgen Receptor Structural and Functional Elements: Role and Regulation in Prostate Cancer Mol. Endocrinol., December 1, 2007; 21(12): 2855 - 2863. [Abstract] [Full Text] [PDF]

				S. M. Dehm, K. M. Regan, L. J. Schmidt, and D. J. Tindall Selective Role of an NH2-Terminal WxxLF Motif for Aberrant Androgen Receptor Activation in Androgen Depletion Independent Prostate Cancer Cells Cancer Res., October 15, 2007; 67(20): 10067 - 10077. [Abstract] [Full Text] [PDF]

				A. Haelens, T. Tanner, S. Denayer, L. Callewaert, and F. Claessens The Hinge Region Regulates DNA Binding, Nuclear Translocation, and Transactivation of the Androgen Receptor Cancer Res., May 1, 2007; 67(9): 4514 - 4523. [Abstract] [Full Text] [PDF]

				C. J Burd, L. M Morey, and K. E Knudsen Androgen receptor corepressors and prostate cancer Endocr. Relat. Cancer, December 1, 2006; 13(4): 979 - 994. [Abstract] [Full Text] [PDF]

				S. M. Dehm and D. J. Tindall Ligand-independent Androgen Receptor Activity Is Activation Function-2-independent and Resistant to Antiandrogens in Androgen Refractory Prostate Cancer Cells J. Biol. Chem., September 22, 2006; 281(38): 27882 - 27893. [Abstract] [Full Text] [PDF]