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.
Mesh Terms:
1-Phosphatidylinositol 3-Kinase, Amino Acid Substitution, Apoptosis, Chromones, Dihydrotestosterone, Enzyme Inhibitors, Gene Expression Regulation, Neoplastic, Humans, Male, Morpholines, Mutagenesis, Site-Directed, Phosphorylation, Prostatic Neoplasms, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-akt, Receptors, Androgen, Recombinant Proteins, Serine, Signal Transduction, Transcriptional Activation, Transfection, Tumor Cells, Cultured
Proc. Natl. Acad. Sci. U.S.A.
Date: Jun. 19, 2001
Download Curated Data For This Publication
73898
Switch View:
  • Interactions 3