Endocrinology, Vol 134, 998-1001, Copyright © 1994 by Endocrine Society

ARTICLES

Agonists, but not antagonists, alter the conformation of the hormone- binding domain of androgen receptor

PJ Kallio, OA Janne and JJ Palvimo

Androgen receptors synthesized by translation in vitro form dimeric aporeceptor complexes with an androgen response element (ARE). Physiological and synthetic androgens elicit a conformational change in the receptor, which increases the mobility of receptor-ARE complexes in gel retardation assays. Neither a steroidal (cyproterone acetate) nor a non-steroidal (casodex) antiandrogen brings about the same effect and, at high concentrations, reverse the action of androgen agonists. When receptor-agonist complexes are subjected to a limited trypsin or chymotrypsin digestion, a protease-resistant 30-kDa fragment corresponding to the entire ligand-binding domain is formed. A similar fragment is not protected in the presence of antiandrogens. The C- terminal origin of the protected region was verified using mutated receptor forms: a mutant with a large N-terminal deletion behaves like the wild-type protein, but the properties of a hormone binding-negative receptor, due to a single-base substitution at codon 807, are not influenced by androgen agonists or antagonists.

This article has been cited by other articles:

				R. P. Pelley, K. Chinnakannu, S. Murthy, F. M. Strickland, M. Menon, Q. P. Dou, E. R. Barrack, and G. P.-V. Reddy Calmodulin-Androgen Receptor (AR) Interaction: Calcium-Dependent, Calpain-Mediated Breakdown of AR in LNCaP Prostate Cancer Cells Cancer Res., December 15, 2006; 66(24): 11754 - 11762. [Abstract] [Full Text] [PDF]

				J. Duff and I. J. McEwan Mutation of Histidine 874 in the Androgen Receptor Ligand-Binding Domain Leads to Promiscuous Ligand Activation and Altered p160 Coactivator Interactions Mol. Endocrinol., December 1, 2005; 19(12): 2943 - 2954. [Abstract] [Full Text] [PDF]

				C. E. Bohl, D. D. Miller, J. Chen, C. E. Bell, and J. T. Dalton Structural Basis for Accommodation of Nonsteroidal Ligands in the Androgen Receptor J. Biol. Chem., November 11, 2005; 280(45): 37747 - 37754. [Abstract] [Full Text] [PDF]

				T. R. Brown Nonsteroidal Selective Androgen Receptors Modulators (SARMs): Designer Androgens with Flexible Structures Provide Clinical Promise Endocrinology, December 1, 2004; 145(12): 5417 - 5419. [Full Text] [PDF]

				B.-C. Jeong, C. Y. Hong, S. Chattopadhyay, J. H. Park, E.-Y. Gong, H.-J. Kim, S.-Y. Chun, and K. Lee Androgen Receptor Corepressor-19 kDa (ARR19), a Leucine-Rich Protein that Represses the Transcriptional Activity of Androgen Receptor through Recruitment of Histone Deacetylase Mol. Endocrinol., January 1, 2004; 18(1): 13 - 25. [Abstract] [Full Text] [PDF]

				D. Yin, Y. He, M. A. Perera, S. S. Hong, C. Marhefka, N. Stourman, L. Kirkovsky, D. D. Miller, and J. T. Dalton Key Structural Features of Nonsteroidal Ligands for Binding and Activation of the Androgen Receptor Mol. Pharmacol., January 1, 2003; 63(1): 211 - 223. [Abstract] [Full Text] [PDF]

				A. J. James, I. U. Agoulnik, J. M. Harris, G. Buchanan, W. D. Tilley, M. Marcelli, D. J. Lamb, and N. L. Weigel A Novel Androgen Receptor Mutant, A748T, Exhibits Hormone Concentration-Dependent Defects in Nuclear Accumulation and Activity Despite Normal Hormone-Binding Affinity Mol. Endocrinol., December 1, 2002; 16(12): 2692 - 2705. [Abstract] [Full Text] [PDF]

				J. Thompson, F. Saatcioglu, O. A. Janne, and J. J. Palvimo Disrupted Amino- and Carboxyl-Terminal Interactions of the Androgen Receptor Are Linked to Androgen Insensitivity Mol. Endocrinol., June 1, 2001; 15(6): 923 - 935. [Abstract] [Full Text] [PDF]

				H Poukka, U Karvonen, N Yoshikawa, H Tanaka, J. Palvimo, and O. Janne The RING finger protein SNURF modulates nuclear trafficking of the androgen receptor J. Cell Sci., January 9, 2000; 113(17): 2991 - 3001. [Abstract] [PDF]

				T. Gao, K. Brantley, E. Bolu, and M. J. McPhaul RFG (ARA70, ELE1) Interacts with the Human Androgen Receptor in a Ligand-Dependent Fashion, but Functions Only Weakly as a Coactivator in Cotransfection Assays Mol. Endocrinol., October 1, 1999; 13(10): 1645 - 1656. [Abstract] [Full Text]

				H. Poukka, P. Aarnisalo, U. Karvonen, J. J. Palvimo, and O. A. Janne Ubc9 Interacts with the Androgen Receptor and Activates Receptor-dependent Transcription J. Biol. Chem., July 2, 1999; 274(27): 19441 - 19446. [Abstract] [Full Text] [PDF]

				M. J. Tetel, P. H. Giangrande, S. A. Leonhardt, D. P. McDonnell, and D. P. Edwards Hormone-Dependent Interaction between the Amino- and Carboxyl-Terminal Domains of Progesterone Receptor in Vitro and in Vivo Mol. Endocrinol., June 1, 1999; 13(6): 910 - 924. [Abstract] [Full Text]

				S. Roux, B. Terouanne, B. Couette, M.-E. Rafestin-Oblin, and J.-C. Nicolas Conformational Change in the Human Glucocorticoid Receptor Induced by Ligand Binding Is Altered by Mutation of Isoleucine 747 by a Threonine J. Biol. Chem., April 9, 1999; 274(15): 10059 - 10065. [Abstract] [Full Text] [PDF]

				A.-M. Moilanen, H. Poukka, U. Karvonen, M. Häkli, O. A. Jänne, and J. J. Palvimo Identification of a Novel RING Finger Protein as a Coregulator in Steroid Receptor-Mediated Gene Transcription Mol. Cell. Biol., September 1, 1998; 18(9): 5128 - 5139. [Abstract] [Full Text]

				U. Karvonen, P. J. Kallio, O. A. Janne, and J. J. Palvimo Interaction of Androgen Receptors with Androgen Response Element in Intact Cells. ROLES OF AMINO- AND CARBOXYL-TERMINAL REGIONS AND THE LIGAND J. Biol. Chem., June 20, 1997; 272(25): 15973 - 15979. [Abstract] [Full Text] [PDF]

				L. V. Nazareth and N. L. Weigel Activation of the Human Androgen Receptor through a Protein Kinase A Signaling Pathway J. Biol. Chem., August 16, 1996; 271(33): 19900 - 19907. [Abstract] [Full Text] [PDF]

				C. W. Kuil, C. A. Berrevoets, and E. Mulder Ligand-induced Conformational Alterations of the Androgen Receptor Analyzed by Limited Trypsinization J. Biol. Chem., November 17, 1995; 270(46): 27569 - 27576. [Abstract] [Full Text] [PDF]

				C.-i. Wong, W. R. Kelce, M. Sar, and E. M. Wilson Androgen Receptor Antagonist versus Agonist Activities of the Fungicide Vinclozolin Relative to Hydroxyflutamide J. Biol. Chem., August 25, 1995; 270(34): 19998 - 20003. [Abstract] [Full Text] [PDF]

				C. E. Petre, Y. B. Wetherill, M. Danielsen, and K. E. Knudsen Cyclin D1: Mechanism and Consequence of Androgen Receptor Co-repressor Activity J. Biol. Chem., January 11, 2002; 277(3): 2207 - 2215. [Abstract] [Full Text] [PDF]