Hormonal Control of Androgen Receptor Function through SIRT1
| Autor: | Anthony A. Sauve, Nagarajan Pattabiraman, Andrew A. Quong, Wei Gu, Maofu Fu, Tianle Yang, Xueping Zhang, Xuanmao Jiao, Fang Wang, Michael J. Powell, Chenguang Wang, Xiaofang Wu, Richard G. Pestell, Timothy G. Pestell, Maria Laura Avantaggiati, Manran Liu |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Models Molecular Transcription Genetic Molecular Sequence Data Cell Cycle Proteins P300-CBP Transcription Factors Biology Cell Line Prostate cancer Sirtuin 1 Genes Reporter medicine Animals Humans Sirtuins p300-CBP Transcription Factors Amino Acid Sequence Molecular Biology Cell Proliferation Histone Acetyltransferases Regulation of gene expression Lysine Prostatic Neoplasms Acetylation Dihydrotestosterone Articles Cell Biology medicine.disease Androgen receptor enzymes and coenzymes (carbohydrates) Gene Expression Regulation Nuclear receptor Receptors Androgen Cancer research Histone deacetylase Signal transduction Peptides hormones hormone substitutes and hormone antagonists Signal Transduction Transcription Factors medicine.drug |
| Zdroj: | Molecular and Cellular Biology. 26:8122-8135 |
| ISSN: | 1098-5549 |
| DOI: | 10.1128/mcb.00289-06 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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