Abstract
Whereas several apoptosis-related proteins have been linked to the antiapoptotic effects of Akt serine-threonine kinase, the search continues to explain the Akt signaling role in promoting cell survival via antiapoptotic effects. Here, we demonstrate that Akt phosphorylates the androgen receptor (AR) at Ser-210 and Ser-790. A mutation at AR Ser-210 results in the reversal of Akt-mediated suppression of AR transactivation. Activation of the phosphatidylinositol-3-OH kinase/Akt pathway results in the suppression of AR target genes, such as p21, and the decrease of androgen/AR-mediated apoptosis, which may involve the inhibition of interaction between AR and AR coregulators. Together, these findings provide a molecular basis for cross-talk between two signaling pathways at the level of Akt and AR-AR coregulators that may help us to better understand the roles of Akt in the androgen/AR-mediated apoptosis.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Substitution
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Androgen Receptor Antagonists
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Apoptosis / drug effects
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Apoptosis / physiology*
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Chromones / pharmacology
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Dihydrotestosterone / pharmacology*
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Enzyme Inhibitors / pharmacology
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Gene Expression Regulation, Neoplastic / drug effects
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Humans
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Male
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Morpholines / pharmacology
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Mutagenesis, Site-Directed
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphorylation
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Prostatic Neoplasms
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Protein Serine-Threonine Kinases / metabolism*
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-akt
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Receptors, Androgen / genetics
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Receptors, Androgen / physiology*
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Recombinant Proteins / metabolism
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Serine
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Signal Transduction
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Transcriptional Activation* / drug effects
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Transfection
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Tumor Cells, Cultured
Substances
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Androgen Receptor Antagonists
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Chromones
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Enzyme Inhibitors
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Morpholines
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Proto-Oncogene Proteins
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Receptors, Androgen
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Recombinant Proteins
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Dihydrotestosterone
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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Serine
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AKT1 protein, human
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt