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

Whereas several apoptosis-related proteins have been linked to the antiapop totic effects of Akt serine-threonine kinase, the search continues to expla in the Akt signaling role in promoting cell survival via antiapoptotic effe cts. 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 phosph atidyl-inositol-3-OH kinase/Akt pathway results in the suppression of AR ta rget genes, such as p21, and the decrease of androgen/AR-mediated apoptosis , which may involve the inhibition of interaction between AR and AR coregul ators, Together, these findings provide a molecular basis for cross-talk be tween two signaling pathways at the level of Akt and AR-AR coregulators tha t may help us to better understand the roles of Akt in the androgen/AR-medi ated apoptosis.