Akt suppresses androgen-induced apoptosis by phosphorylating and inhibiting androgen receptor.
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.
Lin
H K
HK
George Whipple Laboratory for Cancer Research, Department of Pathology, and The Cancer Center, University of Rochester, Rochester, NY 14642, USA.
Yeh
S
S
Kang
H Y
HY
Chang
C
C
D019943:Amino Acid Substitution; D059002:Androgen Receptor Antagonists; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002867:Chromones / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D016297:Mutagenesis, Site-Directed; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011471:Prostatic Neoplasms; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D011944:Receptors, Androgen / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D012694:Serine; D015398:Signal Transduction; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured
D059002:Androgen Receptor Antagonists; D002867:Chromones; D013196:Dihydrotestosterone; D004791:Enzyme Inhibitors; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011944:Receptors, Androgen; D011994:Recombinant Proteins; D012694:Serine; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C494918:AKT1 protein, human