This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fu, M.
Right arrow Articles by Pestell, R. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fu, M.
Right arrow Articles by Pestell, R. G.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, November 2006, p. 8122-8135, Vol. 26, No. 21
0270-7306/06/$08.00+0     doi:10.1128/MCB.00289-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Hormonal Control of Androgen Receptor Function through SIRT1{triangledown}

Maofu Fu,1,{dagger} Manran Liu,1,{dagger} Anthony A. Sauve,2 Xuanmao Jiao,1 Xueping Zhang,1 Xiaofang Wu,1 Michael J. Powell,1 Tianle Yang,2 Wei Gu,3 Maria Laura Avantaggiati,4 Nagarajan Pattabiraman,4 Timothy G. Pestell,1 Fang Wang,5 Andrew A. Quong,1 Chenguang Wang,1 and Richard G. Pestell1*

Department of Cancer Biology and Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107,1 Department of Pharmacology, Weill Medical College, Cornell University, 1300 York Avenue, New York, New York 10021,2 Institute of Cancer Genetics, Department of Pathology, College of Physicians and Surgeons, Columbia University, 1150 St. Nicholas Avenue, New York, New York 10032,3 Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, 3970 Reservoir Road, NW, Washington, D.C. 20057,4 Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 104615

Received 15 February 2006/ Returned for modification 23 March 2006/ Accepted 7 August 2006

The NAD-dependent histone deacetylase Sir2 plays a key role in connecting cellular metabolism with gene silencing and aging. The androgen receptor (AR) is a ligand-regulated modular nuclear receptor governing prostate cancer cellular proliferation, differentiation, and apoptosis in response to androgens, including dihydrotestosterone (DHT). Here, SIRT1 antagonists induce endogenous AR expression and enhance DHT-mediated AR expression. SIRT1 binds and deacetylates the AR at a conserved lysine motif. Human SIRT1 (hSIRT1) repression of DHT-induced AR signaling requires the NAD-dependent catalytic function of hSIRT1 and the AR lysine residues deacetylated by SIRT1. SIRT1 inhibited coactivator-induced interactions between the AR amino and carboxyl termini. DHT-induced prostate cancer cellular contact-independent growth is also blocked by SIRT1, providing a direct functional link between the AR, which is a critical determinant of progression of human prostate cancer, and the sirtuins.

* Corresponding author. Mailing address: Thomas Jefferson University, Department of Cancer Biology, Kimmel Cancer Center, Bluemle Building, Rm. 1050, 233 South 10th St., Philadelphia, PA 19107. Phone: (215) 503-5649. Fax: (215) 503-9334. E-mail: richard.pestell{at}jefferson.edu.

{triangledown} Published ahead of print on 21 August 2006.

{dagger} M. Fu and M. Liu contributed equally to the manuscript.

Molecular and Cellular Biology, November 2006, p. 8122-8135, Vol. 26, No. 21
0270-7306/06/$08.00+0     doi:10.1128/MCB.00289-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Kabra, N., Li, Z., Chen, L., Li, B., Zhang, X., Wang, C., Yeatman, T., Coppola, D., Chen, J. (2009). SirT1 Is an Inhibitor of Proliferation and Tumor Formation in Colon Cancer. J. Biol. Chem. 284: 18210-18217 [Abstract] [Full Text]  
  • Wu, K., Katiyar, S., Witkiewicz, A., Li, A., McCue, P., Song, L.-N., Tian, L., Jin, M., Pestell, R. G. (2009). The Cell Fate Determination Factor Dachshund Inhibits Androgen Receptor Signaling and Prostate Cancer Cellular Growth. Cancer Res. 69: 3347-3355 [Abstract] [Full Text]  
  • Benayoun, B. A., Batista, F., Auer, J., Dipietromaria, A., L'Hote, D., De Baere, E., Veitia, R. A. (2009). Positive and negative feedback regulates the transcription factor FOXL2 in response to cell stress: evidence for a regulatory imbalance induced by disease-causing mutations. Hum Mol Genet 18: 632-644 [Abstract] [Full Text]  
  • Zhao, Y., Takeyama, K.-i., Sawatsubashi, S., Ito, S., Suzuki, E., Yamagata, K., Tanabe, M., Kimura, S., Fujiyama, S., Ueda, T., Murata, T., Matsukawa, H., Shirode, Y., Kouzmenko, A. P., Li, F., Tabata, T., Kato, S. (2009). Corepressive Action of CBP on Androgen Receptor Transactivation in Pericentric Heterochromatin in a Drosophila Experimental Model System. Mol. Cell. Biol. 29: 1017-1034 [Abstract] [Full Text]  
  • Jung-Hynes, B., Nihal, M., Zhong, W., Ahmad, N. (2009). Role of Sirtuin Histone Deacetylase SIRT1 in Prostate Cancer: A TARGET FOR PROSTATE CANCER MANAGEMENT VIA ITS INHIBITION?. J. Biol. Chem. 284: 3823-3832 [Abstract] [Full Text]  
  • Fang, S., Tsang, S., Jones, R., Ponugoti, B., Yoon, H., Wu, S.-Y., Chiang, C.-M., Willson, T. M., Kemper, J. K. (2008). The p300 Acetylase Is Critical for Ligand-activated Farnesoid X Receptor (FXR) Induction of SHP. J. Biol. Chem. 283: 35086-35095 [Abstract] [Full Text]  
  • Venkatesan, B., Ghosh-Choudhury, N., Das, F., Mahimainathan, L., Kamat, A., Kasinath, B. S., Abboud, H. E., Choudhury, G. G. (2008). Resveratrol inhibits PDGF receptor mitogenic signaling in mesangial cells: role of PTP1B. FASEB J. 22: 3469-3482 [Abstract] [Full Text]  
  • Dai, Y., Ngo, D., Jacob, J., Forman, L. W., Faller, D. V. (2008). Prohibitin and the SWI/SNF ATPase subunit BRG1 are required for effective androgen antagonist-mediated transcriptional repression of androgen receptor-regulated genes. Carcinogenesis 29: 1725-1733 [Abstract] [Full Text]  
  • Wang, C., Powell, M. J., Popov, V. M., Pestell, R. G. (2008). Acetylation in Nuclear Receptor Signaling and the Role of Sirtuins. Mol. Endocrinol. 22: 539-545 [Abstract] [Full Text]  
  • Aoyagi, S., Archer, T. K. (2008). Nicotinamide Uncouples Hormone-Dependent Chromatin Remodeling from Transcription Complex Assembly. Mol. Cell. Biol. 28: 30-39 [Abstract] [Full Text]  
  • Heemers, H. V., Tindall, D. J. (2007). Androgen Receptor (AR) Coregulators: A Diversity of Functions Converging on and Regulating the AR Transcriptional Complex. Endocr. Rev. 28: 778-808 [Abstract] [Full Text]  
  • Amat, R., Solanes, G., Giralt, M., Villarroya, F. (2007). SIRT1 Is Involved in Glucocorticoid-mediated Control of Uncoupling Protein-3 Gene Transcription. J. Biol. Chem. 282: 34066-34076 [Abstract] [Full Text]  
  • Yamamoto, H., Schoonjans, K., Auwerx, J. (2007). Sirtuin Functions in Health and Disease. Mol. Endocrinol. 21: 1745-1755 [Abstract] [Full Text]  
  • Dai, Y., Ngo, D., Forman, L. W., Qin, D. C., Jacob, J., Faller, D. V. (2007). Sirtuin 1 Is Required for Antagonist-Induced Transcriptional Repression of Androgen-Responsive Genes by the Androgen Receptor. Mol. Endocrinol. 21: 1807-1821 [Abstract] [Full Text]  
  • Huffman, D. M., Grizzle, W. E., Bamman, M. M., Kim, J.-s., Eltoum, I. A., Elgavish, A., Nagy, T. R. (2007). SIRT1 Is Significantly Elevated in Mouse and Human Prostate Cancer. Cancer Res. 67: 6612-6618 [Abstract] [Full Text]  
  • Stankovic-Valentin, N., Deltour, S., Seeler, J., Pinte, S., Vergoten, G., Guerardel, C., Dejean, A., Leprince, D. (2007). An Acetylation/Deacetylation-SUMOylation Switch through a Phylogenetically Conserved {psi}KXEP Motif in the Tumor Suppressor HIC1 Regulates Transcriptional Repression Activity. Mol. Cell. Biol. 27: 2661-2675 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»