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Androgen Receptor (AR) Coregulators: An Overview

George Whipple Laboratory for Cancer Research, Departments of Pathology, Urology, and Radiation Oncology, University of Rochester, Rochester, New York 14642

Correspondence: Address all correspondence and requests for reprints to: Chawnshang Chang, Ph.D., George Whipple Laboratory for Cancer Research, Department of Pathology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, New York 14642. E-mail: chang{at}urmc.rochester.edu

The biological action of androgens is mediated through the androgen receptor (AR). Androgen-bound AR functions as a transcription factor to regulate genes involved in an array of physiological processes, most notably male sexual differentiation and maturation, and the maintenance of spermatogenesis. The transcriptional activity of AR is affected by coregulators that influence a number of functional properties of AR, including ligand selectivity and DNA binding capacity. As the promoter of target genes, coregulators participate in DNA modification, either directly through modification of histones or indirectly by the recruitment of chromatin-modifying complexes, as well as functioning in the recruitment of the basal transcriptional machinery. Aberrant coregulator activity due to mutation or altered expression levels may be a contributing factor in the progression of diseases related to AR activity, such as prostate cancer. AR demonstrates distinct differences in its interaction with coregulators from other steroid receptors due to differences in the functional interaction between AR domains, possibly resulting in alterations in the dynamic interactions between coregulator complexes.

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				A. Umar, C. A. Berrevoets, N. M. Van, M. van Leeuwen, M. Verbiest, W. J. Kleijer, D. Dooijes, J. A. Grootegoed, S. L. S. Drop, and A. O. Brinkmann Functional Analysis of a Novel Androgen Receptor Mutation, Q902K, in an Individual with Partial Androgen Insensitivity J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 507 - 515. [Abstract] [Full Text] [PDF]

				D.-Y. Lin, H.-I Fang, A.-H. Ma, Y.-S. Huang, Y.-S. Pu, G. Jenster, H.-J. Kung, and H.-M. Shih Negative Modulation of Androgen Receptor Transcriptional Activity by Daxx Mol. Cell. Biol., December 15, 2004; 24(24): 10529 - 10541. [Abstract] [Full Text] [PDF]

				C. Jung, R.-S. Kim, H.-J. Zhang, S.-J. Lee, and M.-H. Jeng HOXB13 Induces Growth Suppression of Prostate Cancer Cells as a Repressor of Hormone-Activated Androgen Receptor Signaling Cancer Res., December 15, 2004; 64(24): 9185 - 9192. [Abstract] [Full Text] [PDF]

				H. Zhu, M. Mazor, Y. Kawano, M. M. Walker, H. Y. Leung, K. Armstrong, J. Waxman, and R. M. Kypta Analysis of Wnt Gene Expression in Prostate Cancer: Mutual Inhibition by WNT11 and the Androgen Receptor Cancer Res., November 1, 2004; 64(21): 7918 - 7926. [Abstract] [Full Text] [PDF]

				K. Steketee, A. C J Ziel-van der Made, H. A G M van der Korput, A. B Houtsmuller, and J. Trapman A bioinformatics-based functional analysis shows that the specifically androgen-regulated gene SARG contains an active direct repeat androgen response element in the first intron J. Mol. Endocrinol., October 1, 2004; 33(2): 477 - 491. [Abstract] [Full Text] [PDF]

				H. J. Dubbink, R. Hersmus, C. S. Verma, H. A. G. M. van der Korput, C. A. Berrevoets, J. van Tol, A. C. J. Ziel-van der Made, A. O. Brinkmann, A. C. W. Pike, and J. Trapman Distinct Recognition Modes of FXXLF and LXXLL Motifs by the Androgen Receptor Mol. Endocrinol., September 1, 2004; 18(9): 2132 - 2150. [Abstract] [Full Text] [PDF]

				Y.-C. Hu, S. Yeh, S.-D. Yeh, E. R. Sampson, J. Huang, P. Li, C.-L. Hsu, H.-J. Ting, H.-K. Lin, L. Wang, et al. Functional Domain and Motif Analyses of Androgen Receptor Coregulator ARA70 and Its Differential Expression in Prostate Cancer J. Biol. Chem., August 6, 2004; 279(32): 33438 - 33446. [Abstract] [Full Text] [PDF]

				Y.-C. Hu, P.-H. Wang, S. Yeh, R.-S. Wang, C. Xie, Q. Xu, X. Zhou, H.-T. Chao, M.-Y. Tsai, and C. Chang Subfertility and defective folliculogenesis in female mice lacking androgen receptor PNAS, August 3, 2004; 101(31): 11209 - 11214. [Abstract] [Full Text] [PDF]

				Y. A. Elhaji, J. Hui Wu, B. Gottlieb, L. K. Beitel, C. Alvarado, G. Batist, and M. A. Trifiro An Examination of How Different Mutations at Arginine 855 of the Androgen Receptor Result in Different Androgen Insensitivity Phenotypes Mol. Endocrinol., August 1, 2004; 18(8): 1876 - 1886. [Abstract] [Full Text] [PDF]

				M. Powzaniuk, S. McElwee-Witmer, R. L. Vogel, T. Hayami, S. J. Rutledge, F. Chen, S.-i. Harada, A. Schmidt, G. A. Rodan, L. P. Freedman, et al. The LATS2/KPM Tumor Suppressor Is a Negative Regulator of the Androgen Receptor Mol. Endocrinol., August 1, 2004; 18(8): 2011 - 2023. [Abstract] [Full Text] [PDF]

				J. Cheng, D. Wang, Z. Wang, and E. T. H. Yeh SENP1 Enhances Androgen Receptor-Dependent Transcription through Desumoylation of Histone Deacetylase 1 Mol. Cell. Biol., July 1, 2004; 24(13): 6021 - 6028. [Abstract] [Full Text] [PDF]

				D. Vanderschueren, L. Vandenput, S. Boonen, M. K. Lindberg, R. Bouillon, and C. Ohlsson Androgens and Bone Endocr. Rev., June 1, 2004; 25(3): 389 - 425. [Abstract] [Full Text] [PDF]

				L. Callewaert, G. Verrijdt, A. Haelens, and F. Claessens Differential Effect of Small Ubiquitin-Like Modifier (SUMO)-ylation of the Androgen Receptor in the Control of Cooperativity on Selective Versus Canonical Response Elements Mol. Endocrinol., June 1, 2004; 18(6): 1438 - 1449. [Abstract] [Full Text] [PDF]

				Y. Liu, B. O. Kim, C. Kao, C. Jung, J. T. Dalton, and J. J. He Tip110, the Human Immunodeficiency Virus Type 1 (HIV-1) Tat-interacting Protein of 110 kDa as a Negative Regulator of Androgen Receptor (AR) Transcriptional Activation J. Biol. Chem., May 21, 2004; 279(21): 21766 - 21773. [Abstract] [Full Text] [PDF]

				C. Chang, Y.-T. Chen, S.-D. Yeh, Q. Xu, R.-S. Wang, F. Guillou, H. Lardy, and S. Yeh Infertility with defective spermatogenesis and hypotestosteronemia in male mice lacking the androgen receptor in Sertoli cells PNAS, May 4, 2004; 101(18): 6876 - 6881. [Abstract] [Full Text] [PDF]

				M. Centrella, T. L. McCarthy, W.-Z. Chang, D. C. Labaree, and R. B. Hochberg Estren (4-Estren-3{alpha},17{beta}-diol) Is a Prohormone that Regulates Both Androgenic and Estrogenic Transcriptional Effects through the Androgen Receptor Mol. Endocrinol., May 1, 2004; 18(5): 1120 - 1130. [Abstract] [Full Text] [PDF]

				Q. Wang, T. S. Udayakumar, T. S. Vasaitis, A. M. Brodie, and J. D. Fondell Mechanistic Relationship between Androgen Receptor Polyglutamine Tract Truncation and Androgen-dependent Transcriptional Hyperactivity in Prostate Cancer Cells J. Biol. Chem., April 23, 2004; 279(17): 17319 - 17328. [Abstract] [Full Text] [PDF]

				C. A. Heinlein and C. Chang Androgen Receptor in Prostate Cancer Endocr. Rev., April 1, 2004; 25(2): 276 - 308. [Abstract] [Full Text] [PDF]

				M. Rahman, H. Miyamoto, and C. Chang Androgen Receptor Coregulators in Prostate Cancer: Mechanisms and Clinical Implications Clin. Cancer Res., April 1, 2004; 10(7): 2208 - 2219. [Full Text] [PDF]

				Y.-H. Lee, H. D. Campbell, and M. R. Stallcup Developmentally Essential Protein Flightless I Is a Nuclear Receptor Coactivator with Actin Binding Activity Mol. Cell. Biol., March 1, 2004; 24(5): 2103 - 2117. [Abstract] [Full Text] [PDF]

				L. Wang, C.-L. Hsu, J. Ni, P.-H. Wang, S. Yeh, P. Keng, and C. Chang Human Checkpoint Protein hRad9 Functions as a Negative Coregulator To Repress Androgen Receptor Transactivation in Prostate Cancer Cells Mol. Cell. Biol., March 1, 2004; 24(5): 2202 - 2213. [Abstract] [Full Text] [PDF]

				C. W. Gregory, X. Fei, L. A. Ponguta, B. He, H. M. Bill, F. S. French, and E. M. Wilson Epidermal Growth Factor Increases Coactivation of the Androgen Receptor in Recurrent Prostate Cancer J. Biol. Chem., February 20, 2004; 279(8): 7119 - 7130. [Abstract] [Full Text] [PDF]

				H. Li, J. H. Kim, S. S. Koh, and M. R. Stallcup Synergistic Effects of Coactivators GRIP1 and {beta}-Catenin on Gene Activation: CROSS-TALK BETWEEN ANDROGEN RECEPTOR AND Wnt SIGNALING PATHWAYS J. Biol. Chem., February 6, 2004; 279(6): 4212 - 4220. [Abstract] [Full Text] [PDF]

				Y. Zhang, Y. Yang, S. Yeh, and C. Chang ARA67/PAT1 Functions as a Repressor To Suppress Androgen Receptor Transactivation Mol. Cell. Biol., February 1, 2004; 24(3): 1044 - 1057. [Abstract] [Full Text] [PDF]