Not sure how viable or effective this will be in the future but thought it was interesting that if you could increase Transcription at the G1/S cell transition you might be able to increase protein synthesis with the inhibition of histone deacetylases and activators, especially if we can target specific cells. I would be interested to hear from someone who has more knowledge in this area to see if this would be an effective idea or too minimal to make a real difference. The full study is too big to put on here but I believe the link is attached. Discussion is welcome.
Originally published In Press as doi:10.1074/jbc.M112134200 on June 7, 2002
J. Biol. Chem., Vol. 277, Issue 33, 29719-29729, August 16, 2002
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Articles by Martinez, E. D.
Articles by Danielsen, M.
Loss of Androgen Receptor Transcriptional Activity at the G1/S Transition*
Elisabeth D. Martinez and Mark Danielsen
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.
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* 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: [email protected].
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Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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