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Volume 270, Number 50, Issue of December 15, 1995 pp. 29983-29990
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
Evidence for an Anti-parallel Orientation of the Ligand-activated Human Androgen Receptor Dimer

(Received for publication, June 8, 1995; and in revised form, September 20, 1995)

Elizabeth Langley Zhoug-xun Zhou Elizabeth M. Wilson

Domain interactions of the human androgen receptor (AR) dimer were investigated using a protein-protein interaction assay in which the NH(2)- and carboxyl-terminal regions of human AR were fused to the Saccharomyces cerevisiae GAL4 DNA-binding domain and herpes simplex virus VP16 transactivation domain to produce chimeric proteins. Transcriptional activation of a GAL4 luciferase reporter vector up to 100-fold was greater than Fos/Jun leucine zipper binding, indicating stable AR interaction between AR NH(2)-terminal residues 1-503 and steroid-binding domain residues 624-919 that was specific for and dependent on androgen binding to the steroid-binding domain and was inhibited by anti-androgen binding. Deletion mutagenesis within the NH(2)-terminal region indicated transactivation domain residues 142-337 were not required for dimerization, whereas deletions near the NH(2) terminus (Delta14-150) or NH(2)-terminal to the DNA-binding domain (Delta339-499) reduced or eliminated the AR interaction, respectively. An NH(2)-/NH(2)-terminal interaction was also observed, but no interaction was detected between ligand-free or bound steroid-binding domains. The results indicate that high affinity androgen binding promotes interactions between the NH(2)-terminal and steroid-binding domains of human AR, raising the possibility of an androgen-induced anti-parallel AR dimer.




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Mutational Analysis of the Androgen Receptor AF-2 (Activation Function 2) Core Domain Reveals Functional and Mechanistic Differences of Conserved Residues Compared with Other Nuclear Receptors
Mol. Endocrinol., October 1, 2000; 14(10): 1603 - 1617.
[Abstract] [Full Text]


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EndocrinologyHome page
J.-a. Tan, S. H. Hall, P. Petrusz, and F. S. French
Thyroid Receptor Activator Molecule, TRAM-1, Is an Androgen Receptor Coactivator
Endocrinology, September 1, 2000; 141(9): 3440 - 3450.
[Abstract] [Full Text] [PDF]


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JCBHome page
A. Yamamoto, Y. Hashimoto, K. Kohri, E. Ogata, S.-a. Kato, K. Ikeda, and M. Nakanishi
Cyclin E As a Coactivator of the Androgen Receptor
J. Cell Biol., August 21, 2000; 150(4): 873 - 880.
[Abstract] [Full Text] [PDF]


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Mol. Endocrinol.Home page
J. Lim, F. J. Ghadessy, A. A. R. Abdullah, L. Pinsky, M. Trifiro, and E. L. Yong
Human Androgen Receptor Mutation Disrupts Ternary Interactions between Ligand, Receptor Domains, and the Coactivator TIF2 (Transcription Intermediary Factor 2)
Mol. Endocrinol., August 1, 2000; 14(8): 1187 - 1197.
[Abstract] [Full Text]


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Mol. Endocrinol.Home page
H. Fuse, H. Kitagawa, and S. Kato
Characterization of Transactivational Property and Coactivator Mediation of Rat Mineralocorticoid Receptor Activation Function-1 (AF-1)
Mol. Endocrinol., June 1, 2000; 14(6): 889 - 899.
[Abstract] [Full Text]


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Mol. Cell. Biol.Home page
S.-M. Huang and M. R. Stallcup
Mouse Zac1, a Transcriptional Coactivator and Repressor for Nuclear Receptors
Mol. Cell. Biol., March 1, 2000; 20(5): 1855 - 1867.
[Abstract] [Full Text]


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Toxicol SciHome page
T. J. Schrader and G. M. Cooke
Examination of Selected Food Additives and Organochlorine Food Contaminants for Androgenic Activity in Vitro
Toxicol. Sci., February 1, 2000; 53(2): 278 - 288.
[Abstract] [Full Text] [PDF]


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Hum Mol GenetHome page
R. A. Irvine, H. Ma, M. C. Yu, R. K. Ross, M. R. Stallcup, and G. A. Coetzee
Inhibition of p160-mediated coactivation with increasing androgen receptor polyglutamine length
Hum. Mol. Genet., January 22, 2000; 9(2): 267 - 274.
[Abstract] [Full Text] [PDF]


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Mol. Endocrinol.Home page
J.-a. Tan, S. H. Hall, K. G. Hamil, G. Grossman, P. Petrusz, J. Liao, K. Shuai, and F. S. French
Protein Inhibitor of Activated STAT-1 (Signal Transducer and Activator of Transcription-1) Is a Nuclear Receptor Coregulator Expressed in Human Testis
Mol. Endocrinol., January 1, 2000; 14(1): 14 - 26.
[Abstract] [Full Text]


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J. Biol. Chem.Home page
B. He, J. A. Kemppainen, J. J. Voegel, H. Gronemeyer, and E. M. Wilson
Activation Function 2 in the Human Androgen Receptor Ligand Binding Domain Mediates Interdomain Communication with the NH2-terminal Domain
J. Biol. Chem., December 24, 1999; 274(52): 37219 - 37225.
[Abstract] [Full Text] [PDF]


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Mol. Cell. Biol.Home page
C. L. Bevan, S. Hoare, F. Claessens, D. M. Heery, and M. G. Parker
The AF1 and AF2 Domains of the Androgen Receptor Interact with Distinct Regions of SRC1
Mol. Cell. Biol., December 1, 1999; 19(12): 8383 - 8392.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
W. Huang, Y. Shostak, P. Tarr, C. Sawyers, and M. Carey
Cooperative Assembly of Androgen Receptor into a Nucleoprotein Complex That Regulates the Prostate-specific Antigen Enhancer
J. Biol. Chem., September 3, 1999; 274(36): 25756 - 25768.
[Abstract] [Full Text] [PDF]


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Mol. Cell. Biol.Home page
P. Alen, F. Claessens, G. Verhoeven, W. Rombauts, and B. Peeters
The Androgen Receptor Amino-Terminal Domain Plays a Key Role in p160 Coactivator-Stimulated Gene Transcription
Mol. Cell. Biol., September 1, 1999; 19(9): 6085 - 6097.
[Abstract] [Full Text] [PDF]


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Mol. Cell. Biol.Home page
H. Ma, H. Hong, S.-M. Huang, R. A. Irvine, P. Webb, P. J. Kushner, G. A. Coetzee, and M. R. Stallcup
Multiple Signal Input and Output Domains of the 160-Kilodalton Nuclear Receptor Coactivator Proteins
Mol. Cell. Biol., September 1, 1999; 19(9): 6164 - 6173.
[Abstract] [Full Text] [PDF]


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Mol. Endocrinol.Home page
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]


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J. Biol. Chem.Home page
X. Sui, K. S. Bramlett, M. C. Jorge, D. A. Swanson, A. C. von Eschenbach, and G. Jenster
Specific Androgen Receptor Activation by an Artificial Coactivator
J. Biol. Chem., April 2, 1999; 274(14): 9449 - 9454.
[Abstract] [Full Text] [PDF]


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Mol. Endocrinol.Home page
J. A. Kemppainen, E. Langley, C.-i. Wong, K. Bobseine, W. R. Kelce, and E. M. Wilson
Distinguishing Androgen Receptor Agonists and Antagonists: Distinct Mechanisms of Activation by Medroxyprogesterone Acetate and Dihydrotestosterone
Mol. Endocrinol., March 1, 1999; 13(3): 440 - 454.
[Abstract] [Full Text]


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Mol. Endocrinol.Home page
S. A. Leonhardt, M. Altmann, and D. P. Edwards
Agonist and Antagonists Induce Homodimerization and Mixed Ligand Heterodimerization of Human Progesterone Receptors in Vivo by a Mammalian Two-Hybrid Assay
Mol. Endocrinol., December 1, 1998; 12(12): 1914 - 1930.
[Abstract] [Full Text]


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J. Biol. Chem.Home page
A. Scheller, E. Hughes, K. L. Golden, and D. M. Robins
Multiple Receptor Domains Interact to Permit, or Restrict, Androgen-specific Gene Activation
J. Biol. Chem., September 11, 1998; 273(37): 24216 - 24222.
[Abstract] [Full Text] [PDF]


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Mol. Endocrinol.Home page
C. A. Berrevoets, P. Doesburg, K. Steketee, J. Trapman, and A. O. Brinkmann
Functional Interactions of the AF-2 Activation Domain Core Region of the Human Androgen Receptor with the Amino-Terminal Domain and with the Transcriptional Coactivator TIF2 (Transcriptional Intermediary Factor 2)
Mol. Endocrinol., August 1, 1998; 12(8): 1172 - 1183.
[Abstract] [Full Text]


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J. Biol. Chem.Home page
E. Langley, J. A. Kemppainen, and E. M. Wilson
Intermolecular NH2-/Carboxyl-terminal Interactions in Androgen Receptor Dimerization Revealed by Mutations That Cause Androgen Insensitivity
J. Biol. Chem., January 2, 1998; 273(1): 92 - 101.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
T. Ikonen, J. J. Palvimo, and O. A. Janne
Interaction between the Amino- and Carboxyl-terminal Regions of the Rat Androgen Receptor Modulates Transcriptional Activity and Is Influenced by Nuclear Receptor Coactivators
J. Biol. Chem., November 21, 1997; 272(47): 29821 - 29828.
[Abstract] [Full Text] [PDF]


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Mol. Endocrinol.Home page
L. L. Heckert, E. M. Wilson, and J. H. Nilson
Transcriptional Repression of the {alpha}-Subunit Gene by Androgen Receptor Occurs Independently of DNA Binding but Requires the DNA-Binding and Ligand-Binding Domains of the Receptor
Mol. Endocrinol., September 1, 1997; 11(10): 1497 - 1506.
[Abstract] [Full Text]


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Mol. Endocrinol.Home page
M. J. Tetel, S. Jung, P. Carbajo, T. Ladtkow, D. F. Skafar, and D. P. Edwards
Hinge and Amino-Terminal Sequences Contribute to Solution Dimerization of Human Progesterone Receptor
Mol. Endocrinol., July 1, 1997; 11(8): 1114 - 1128.
[Abstract] [Full Text]


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J. Biol. Chem.Home page
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]


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J. Biol. Chem.Home page
Z. Zhou, J. L. Corden, and T. R. Brown
Identification and Characterization of a Novel Androgen Response Element Composed of a Direct Repeat
J. Biol. Chem., March 28, 1997; 272(13): 8227 - 8235.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
N. L. Chamberlain, D. C. Whitacre, and R. L. Miesfeld
Delineation of Two Distinct Type 1Activation Functions in the Androgen Receptor Amino-terminal Domain
J. Biol. Chem., October 25, 1996; 271(43): 26772 - 26778.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
A. Bubulya, S. C. Wise, X.-Q. Shen, L. A. Burmeister, and L. Shemshedini
c-Jun Can Mediate Androgen Receptor-induced Transactivation
J. Biol. Chem., October 4, 1996; 271(40): 24583 - 24589.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
M. Xu, P. K. Chakraborti, M. J. Garabedian, K. R. Yamamoto, and S. S. Simons Jr.
Modular Structure of Glucocorticoid Receptor Domains Is Not Equivalent to Functional Independence. STABILITY AND ACTIVITY OF THE STEROID BINDING DOMAIN ARE CONTROLLED BY SEQUENCES IN SEPARATE DOMAINS
J. Biol. Chem., August 30, 1996; 271(35): 21430 - 21438.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
J. P. Aumais, H. S. Lee, C. DeGannes, J. Horsford, and J. H. White
Function of Directly Repeated Half-sites as Response Elements for Steroid Hormone Receptors
J. Biol. Chem., May 24, 1996; 271(21): 12568 - 12577.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
B. He, J. A. Kemppainen, and E. M. Wilson
FXXLF and WXXLF Sequences Mediate the NH2-terminal Interaction with the Ligand Binding Domain of the Androgen Receptor
J. Biol. Chem., July 21, 2000; 275(30): 22986 - 22994.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
J. Rao, P. Lee, S. Benzeno, C. Cardozo, J. Albertus, D. M. Robins, and A. J. Caplan
Functional Interaction of Human Cdc37 with the Androgen Receptor but Not with the Glucocorticoid Receptor
J. Biol. Chem., February 16, 2001; 276(8): 5814 - 5820.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
K. Takahashi, T. Taira, T. Niki, C. Seino, S. M. M. Iguchi-Ariga, and H. Ariga
DJ-1 Positively Regulates the Androgen Receptor by Impairing the Binding of PIASxalpha to the Receptor
J. Biol. Chem., September 28, 2001; 276(40): 37556 - 37563.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
T. Slagsvold, I. Kraus, K. Fronsdal, and F. Saatcioglu
DNA Binding-independent Transcriptional Activation by the Androgen Receptor through Triggering of Coactivators
J. Biol. Chem., August 10, 2001; 276(33): 31030 - 31036.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
X. Wang, S. Yeh, G. Wu, C.-L. Hsu, L. Wang, T. Chiang, Y. Yang, Y. Guo, and C. Chang
Identification and Characterization of a Novel Androgen Receptor Coregulator ARA267-alpha in Prostate Cancer Cells
J. Biol. Chem., October 26, 2001; 276(44): 40417 - 40423.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
A. Bubulya, S.-Y. Chen, C. J. Fisher, Z. Zheng, X.-Q. Shen, and L. Shemshedini
c-Jun Potentiates the Functional Interaction between the Amino and Carboxyl Termini of the Androgen Receptor
J. Biol. Chem., November 21, 2001; 276(48): 44704 - 44711.
[Abstract] [Full Text] [PDF]




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