|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 28, 25631-25639, July 12, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Laboratories for Reproductive Biology and the Departments
of Pediatrics and Biochemistry and Biophysics, University of North
Carolina, Chapel Hill, North Carolina 27599-7500
The agonist-induced androgen receptor
NH2- and COOH-terminal (N/C) interaction is mediated
by the FXXLF and WXXLF NH2-terminal motifs. Here we demonstrate that agonist-dependent
transactivation of prostate-specific antigen (PSA) and probasin
enhancer/promoter regions requires the N/C interaction, whereas the
sex-limited protein gene and mouse mammary tumor virus long terminal
repeat do not. Transactivation of PSA and probasin response
regions also depends on activation function 1 (AF1) in the
NH2-terminal region but can be increased by binding an
overexpressed p160 coactivator to activation function 2 (AF2) in the
ligand binding domain. The dependence of the PSA and probasin
enhancer/promoters on the N/C interaction for transactivation allowed
us to demonstrate that in the presence of androgen, the
WXXLF motif with the sequence 433WHTLF437 contributes as an inhibitor to AR
transactivation. We further show that like the FXXLF and
LXXLL motifs, the WXXLF motif interacts in the
presence of androgen with AF2 in the ligand binding domain. Sequence
comparisons among species indicate greater conservation of the
FXXLF motif compared with the WXXLF motif,
paralleling the functional significance of these binding motifs. The
data provide evidence for promoter-specific differences in the
requirement for the androgen receptor N/C interaction and in the
contributions of AF1 and AF2 in androgen-induced gene regulation.
Dependence of Selective Gene Activation on the Androgen Receptor
NH2- and COOH-terminal Interaction*
*
The work was supported by Public Health Service Grant
HD16910 from the National Institute of Child Health and Development, by
cooperative agreement U54-HD35041 as part of the Specialized Cooperative Centers Program in Reproductive Research of National Institutes of Health; by the United States Army Medical Research and
Material Command Grant DAMD17-00-1-0094; and by the International Training and Research in Population and Health Program supported by the
Fogarty International Center and NICHD, National Institutes of Health.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Laboratories for
Reproductive Biology, Rm. 374 Medical Sciences Research Bldg., CB 7500, University of North Carolina, Chapel Hill, NC 27599. Tel.:
919-966-5168; Fax: 919-966-2203; E-mail: emw@med.unc.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  A. R. Karpf, S. Bai, S. R. James, J. L. Mohler, and E. M. Wilson Increased Expression of Androgen Receptor Coregulator MAGE-11 in Prostate Cancer by DNA Hypomethylation and Cyclic AMP Mol. Cancer Res., April 1, 2009; 7(4): 523 - 535. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. E. Rosenblatt and K. L. Burnstein Inhibition of Androgen Receptor Transcriptional Activity as a Novel Mechanism of Action of Arsenic Mol. Endocrinol., March 1, 2009; 23(3): 412 - 421. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. U. Agoulnik, W. E. Bingman III, M. Nakka, W. Li, Q. Wang, X. S. Liu, M. Brown, and N. L. Weigel Target Gene-Specific Regulation of Androgen Receptor Activity by p42/p44 Mitogen-Activated Protein Kinase Mol. Endocrinol., November 1, 2008; 22(11): 2420 - 2432. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. A. O'Mahony, M. P. Steinkamp, M. A. Albertelli, M. Brogley, H. Rehman, and D. M. Robins Profiling Human Androgen Receptor Mutations Reveals Treatment Effects in a Mouse Model of Prostate Cancer Mol. Cancer Res., November 1, 2008; 6(11): 1691 - 1701. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Deeb, J. Jaaskelainen, M. Dattani, H. C. Whitaker, C. Costigan, and I. A. Hughes A Novel Mutation in the Human Androgen Receptor Suggests a Regulatory Role for the Hinge Region in Amino-Terminal and Carboxy-Terminal Interactions J. Clin. Endocrinol. Metab., October 1, 2008; 93(10): 3691 - 3696. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kaulfuss, M. Grzmil, B. Hemmerlein, P. Thelen, S. Schweyer, J. Neesen, L. Bubendorf, A. G. Glass, H. Jarry, B. Auber, et al. Leupaxin, a Novel Coactivator of the Androgen Receptor, Is Expressed in Prostate Cancer and Plays a Role in Adhesion and Invasion of Prostate Carcinoma Cells Mol. Endocrinol., July 1, 2008; 22(7): 1606 - 1621. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 H. V. Heemers and D. J. Tindall Androgen Receptor (AR) Coregulators: A Diversity of Functions Converging on and Regulating the AR Transcriptional Complex Endocr. Rev., December 1, 2007; 28(7): 778 - 808. [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]
|
|
|
|
 |
|
 E. B. Askew, R. T. Gampe Jr., T. B. Stanley, J. L. Faggart, and E. M. Wilson Modulation of Androgen Receptor Activation Function 2 by Testosterone and Dihydrotestosterone J. Biol. Chem., August 31, 2007; 282(35): 25801 - 25816. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Lu, A. Wang, S. Lu, and Z. Dong A novel synthetic compound that interrupts androgen receptor signaling in human prostate cancer cells Mol. Cancer Ther., July 1, 2007; 6(7): 2057 - 2064. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. N. Miner, W. Chang, M. S. Chapman, P. D. Finn, M. H. Hong, F. J. Lopez, K. B. Marschke, J. Rosen, W. Schrader, R. Turner, et al. An Orally Active Selective Androgen Receptor Modulator Is Efficacious on Bone, Muscle, and Sex Function with Reduced Impact on Prostate Endocrinology, January 1, 2007; 148(1): 363 - 373. [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]
|
|
|
|
|
|
D. J. van de Wijngaart, M. E. van Royen, R. Hersmus, A. C. W. Pike, A. B. Houtsmuller, G. Jenster, J. Trapman, and H. J. Dubbink Novel FXXFF and FXXMF Motifs in Androgen Receptor Cofactors Mediate High Affinity and Specific Interactions with the Ligand-binding Domain J. Biol. Chem., July 14, 2006; 281(28): 19407 - 19416. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Kazmin, T. Prytkova, C. E. Cook, R. Wolfinger, T.-M. Chu, D. Beratan, J. D. Norris, C.-y. Chang, and D. P. McDonnell Linking Ligand-Induced Alterations in Androgen Receptor Structure to Differential Gene Expression: A First Step in the Rational Design of Selective Androgen Receptor Modulators Mol. Endocrinol., June 1, 2006; 20(6): 1201 - 1217. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J Jaaskelainen, A Deeb, J W Schwabe, N P Mongan, H Martin, and I A Hughes Human androgen receptor gene ligand-binding-domain mutations leading to disrupted interaction between the N- and C-terminal domains. J. Mol. Endocrinol., April 1, 2006; 36(2): 361 - 368. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Li, J. Fu, C. Toumazou, H.-G. Yoon, and J. Wong A Role of the Amino-Terminal (N) and Carboxyl-Terminal (C) Interaction in Binding of Androgen Receptor to Chromatin Mol. Endocrinol., April 1, 2006; 20(4): 776 - 785. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. He, R. T. Gampe Jr., A. T. Hnat, J. L. Faggart, J. T. Minges, F. S. French, and E. M. Wilson Probing the Functional Link between Androgen Receptor Coactivator and Ligand-binding Sites in Prostate Cancer and Androgen Insensitivity J. Biol. Chem., March 10, 2006; 281(10): 6648 - 6663. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. H. Baek, K. A. Ohgi, C. A. Nelson, D. Welsbie, C. Chen, C. L. Sawyers, D. W. Rose, and M. G. Rosenfeld Ligand-specific allosteric regulation of coactivator functions of androgen receptor in prostate cancer cells PNAS, February 28, 2006; 103(9): 3100 - 3105. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Burd, C. E. Petre, L. M. Morey, Y. Wang, M. P. Revelo, C. A. Haiman, S. Lu, C. M. Fenoglio-Preiser, J. Li, E. S. Knudsen, et al. Cyclin D1b variant influences prostate cancer growth through aberrant androgen receptor regulation PNAS, February 14, 2006; 103(7): 2190 - 2195. [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]
|
|
|
|
|
|
F. Schaufele, X. Carbonell, M. Guerbadot, S. Borngraeber, M. S. Chapman, A. A. K. Ma, J. N. Miner, and M. I. Diamond The structural basis of androgen receptor activation: Intramolecular and intermolecular amino-carboxy interactions PNAS, July 12, 2005; 102(28): 9802 - 9807. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Brodie and I. J McEwan Intra-domain communication between the N-terminal and DNA-binding domains of the androgen receptor: modulation of androgen response element DNA binding J. Mol. Endocrinol., June 1, 2005; 34(3): 603 - 615. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Estebanez-Perpina, J. M. R. Moore, E. Mar, E. Delgado-Rodrigues, P. Nguyen, J. D. Baxter, B. M. Buehrer, P. Webb, R. J. Fletterick, and R. K. Guy The Molecular Mechanisms of Coactivator Utilization in Ligand-dependent Transactivation by the Androgen Receptor J. Biol. Chem., March 4, 2005; 280(9): 8060 - 8068. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. L Golden, J. D Marsh, Y. Jiang, and J. Moulden Acute actions of testosterone on contractile function of isolated rat ventricular myocytes Eur. J. Endocrinol., March 1, 2005; 152(3): 479 - 483. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Burd, C. E. Petre, H. Moghadam, E. M. Wilson, and K. E. Knudsen Cyclin D1 Binding to the Androgen Receptor (AR) NH2-Terminal Domain Inhibits Activation Function 2 Association and Reveals Dual Roles for AR Corepression Mol. Endocrinol., March 1, 2005; 19(3): 607 - 620. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bai, B. He, and E. M. Wilson Melanoma Antigen Gene Protein MAGE-11 Regulates Androgen Receptor Function by Modulating the Interdomain Interaction Mol. Cell. Biol., February 15, 2005; 25(4): 1238 - 1257. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Sonneveld, H. J. Jansen, J. A. C. Riteco, A. Brouwer, and B. van der Burg Development of Androgen- and Estrogen-Responsive Bioassays, Members of a Panel of Human Cell Line-Based Highly Selective Steroid-Responsive Bioassays Toxicol. Sci., January 1, 2005; 83(1): 136 - 148. [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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
B. He, S. Bai, A. T. Hnat, R. I. Kalman, J. T. Minges, C. Patterson, and E. M. Wilson An Androgen Receptor NH2-terminal Conserved Motif Interacts with the COOH Terminus of the Hsp70-interacting Protein (CHIP) J. Biol. Chem., July 16, 2004; 279(29): 30643 - 30653. [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]
|
|
|
|
|
|
C. E. Petre-Draviam, S. L. Cook, C. J. Burd, T. W. Marshall, Y. B. Wetherill, and K. E. Knudsen Specificity of Cyclin D1 for Androgen Receptor Regulation Cancer Res., August 15, 2003; 63(16): 4903 - 4913. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-L. Hsu, Y.-L. Chen, S. Yeh, H.-J. Ting, Y.-C. Hu, H. Lin, X. Wang, and C. Chang The Use of Phage Display Technique for the Isolation of Androgen Receptor Interacting Peptides with (F/W)XXL(F/W) and FXXLY New Signature Motifs J. Biol. Chem., June 20, 2003; 278(26): 23691 - 23698. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. He and E. M. Wilson Electrostatic Modulation in Steroid Receptor Recruitment of LXXLL and FXXLF Motifs Mol. Cell. Biol., March 15, 2003; 23(6): 2135 - 2150. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Kumar and E. B. Thompson Transactivation Functions of the N-Terminal Domains of Nuclear Hormone Receptors: Protein Folding and Coactivator Interactions Mol. Endocrinol., January 1, 2003; 17(1): 1 - 10. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Christiaens, C. L. Bevan, L. Callewaert, A. Haelens, G. Verrijdt, W. Rombauts, and F. Claessens Characterization of the Two Coactivator-interacting Surfaces of the Androgen Receptor and Their Relative Role in Transcriptional Control* J. Biol. Chem., December 13, 2002; 277(51): 49230 - 49237. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |