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

HK Lin, S Yeh, HY Kang… - Proceedings of the …, 2001 - National Acad Sciences
HK Lin, S Yeh, HY Kang, C Chang
Proceedings of the National Academy of Sciences, 2001National Acad Sciences
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 …
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.
National Acad Sciences