|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 33, 29719-29729, August 16, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Department of Biochemistry and Molecular Biology,
Georgetown University School of Medicine,
Washington, D. C. 20007
Androgens are essential for the differentiation,
growth, and maintenance of male-specific organs. The effects of
androgens in cells are mediated by the androgen receptor (AR), a member of the nuclear receptor superfamily of transcription factors. Recently,
transient transfection studies have shown that overexpression of cell
cycle regulatory proteins affects the transcriptional activity of the
AR. In this report, we characterize the transcriptional activity of
endogenous AR through the cell cycle. We demonstrate that in G0, AR
enhances transcription from an integrated steroid-responsive mouse
mammary tumor virus promoter and also from an integrated androgen-specific probasin promoter. This activity is strongly reduced
or abolished at the G1/S boundary. In S phase, the
receptor regains activity, indicating that there is a transient
regulatory event that inactivates the AR at the G1/S
transition. This regulation is specific for the AR, since the related
glucocorticoid receptor is transcriptionally active at the
G1/S boundary. Not all of the effects of androgens are
blocked, however, since androgens retain the ability to increase AR
protein levels. The transcriptional inactivity of the AR at the
G1/S junction coincides with a decrease in AR protein
level, although activity can be partly rescued without an increase in
receptor. Inhibition of histone deacetylases brings about this partial
restoration of AR activity at the G1/S boundary, demonstrating the involvement of acetylation pathways in the cell cycle
regulation of AR transcriptional activity. Finally, a model is proposed
that explains the inactivity of the AR at the G1/S transition by integrating receptor levels, the action of cell cycle
regulators, and the contribution of histone
acetyltransferase-containing coactivators.
Loss of Androgen Receptor Transcriptional Activity at the
G1/S Transition*
*
This work was supported by Department of Defense predoctoral
fellowship DAMD17-99-1-9199 (to E. M.) and by American Heart Association (Mid-Atlantic) Grant 9951256U (to M. D.).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: Dept. of Biochemistry
and Molecular Biology, Georgetown University School of Medicine, Basic
Science Bldg. Rm. 355, 3900 Reservoir Rd., NW, Washington, D. C.
20007. Tel.: 202-687-4169; Fax: 202-687-7186; E-mail:
dan@bc.georgetown.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:
|
|
 |
|
  W. Lin, J. Wu, H. Dong, D. Bouck, F.-Y. Zeng, and T. Chen Cyclin-dependent Kinase 2 Negatively Regulates Human Pregnane X Receptor-mediated CYP3A4 Gene Expression in HepG2 Liver Carcinoma Cells J. Biol. Chem., November 7, 2008; 283(45): 30650 - 30657. [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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 P. J. Martin, V. Lardeux, and P. Lefebvre The proliferating cell nuclear antigen regulates retinoic acid receptor transcriptional activity through direct protein-protein interaction Nucleic Acids Res., July 29, 2005; 33(13): 4311 - 4321. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Narayanan, D. P. Edwards, and N. L. Weigel Human Progesterone Receptor Displays Cell Cycle-Dependent Changes in Transcriptional Activity Mol. Cell. Biol., April 15, 2005; 25(8): 2885 - 2898. [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]
|
|
|
|
|
|
R. Narayanan, A. A. Adigun, D. P. Edwards, and N. L. Weigel Cyclin-Dependent Kinase Activity Is Required for Progesterone Receptor Function: Novel Role for Cyclin A/Cdk2 as a Progesterone Receptor Coactivator Mol. Cell. Biol., January 1, 2005; 25(1): 264 - 277. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Yang, C.-M. Chen, P. Yan, T. H-M. Huang, H. Shi, M. Burger, I. Nimmrich, S. Maier, K. Berlin, and C. W. Caldwell The Androgen Receptor Gene is Preferentially Hypermethylated in Follicular Non-Hodgkin's Lymphomas Clin. Cancer Res., September 15, 2003; 9(11): 4034 - 4042. [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]
|
|
|
|
 |
|
 O. M. Tirado, E. D. Martinez, O. C. Rodriguez, M. Danielsen, D. M. Selva, J. Reventos, F. Munell, and C. A. Suarez-Quian Methoxyacetic Acid Disregulation of Androgen Receptor and Androgen-Binding Protein Expression in Adult Rat Testis Biol Reprod, April 1, 2003; 68(4): 1437 - 1446. [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 |