Gi and RGS proteins provide biochemical control of androgen receptor nuclear exclusion

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• 作者：Avi Rimler (1)
  Ralf Jockers (2)
  Zipora Lupowitz (1)
  Nava Zisapel (1)
  
• 关键词：RGS10 ; RGS4 ; RGS2 ; androgen receptor ; nuclear localization ; PKC ; calcium ; melatonin ; cGMP
• 刊名：Journal of Molecular Neuroscience
• 出版年：2007
• 出版时间：January 2007
• 年：2007
• 卷：31
• 期：1
• 页码：1-12
• 全文大小：2281KB
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• 作者单位：Avi Rimler (1)
  Ralf Jockers (2)
  Zipora Lupowitz (1)
  Nava Zisapel (1)
  
  1. Department of Neurobiochemistry, The George S. Wise Faculty of Life Sciences, Tel Aviv University, 69978, Tel Aviv, Israel
  2. Institut National de la Santé et de la Recherche Médicale (INSERM) U. 567, Centre National de la Recherche Scientifique (CNRS) UMR 8104 and Universite Paris V, Institut Cochin, Department of Cell Biology, F-75014, Paris, France
  

文摘

Nuclear localization of androgen receptors (ARs) is essential for their activity. Melatonin induces AR nuclear exclusion via increase in cGMP, calcium, and protein kinase C (PKC) activation, presumably through G-protein(s). The effects of regulators of G-protein signaling (RGS) on AR localization were studied in AR-expressing PC3 cells. Gi-specific RGS10 inhibited melatonin but not cGMP-induced AR nuclear exclusion, independent of androgen. No evidence for Gq activation by melatonin was found. However, Gi/Gq-selective RGS4 inhibited AR nuclear exclusion downstream of PKC activation—an effect that was abrogated by constitutively active Gq. RGS10 and RGS4, but not RGS2, ablated the inhibitory effects of melatonin on AR reporter gene activity. For the first time, these data show regulation by Gi and Gi-specific RGS protein-mediated AR nuclear exclusion, which is potentially important in the treatment of AR-dependent cancers and neurodegenerative disorders. They also reveal a role for a Gq protein downstream of PKC activation in AR nuclear localization.