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Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7200-5. Epub 2001 Jun 12.

Akt suppresses androgen-induced apoptosis by phosphorylating and inhibiting androgen receptor.

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George Whipple Laboratory for Cancer Research, Department of Pathology, and The Cancer Center, University of Rochester, Rochester, NY 14642, USA.


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.

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