XXXX methylation of @entity588 antagonist of cell death ( @entity1835 ) counteracts its phosphorylation and inactivation by Akt.

@entity522 @entity588 @entity32656 @entity1836 @entity534 @entity1835 @entity369
Protein @entity369 methylation is a common posttranslational modification catalyzed by a family of the protein @entity369 methyltransferases (PRMTs). We have previously reported that @entity32656 methylates Forkhead box O transcription factors at two @entity369 residues within an Akt consensus phosphorylation motif (RxRxxS/T), and that this methylation blocks Akt-mediated phosphorylation of the transcription factors. These findings led us to hypothesize that the functional crosstalk between @entity369 methylation and phosphorylation could be extended to other Akt target proteins as well as Forkhead box O proteins. Here we identify @entity588 antagonist of cell death ( @entity1835 ) as an additional substrate for @entity32656 among several Akt target proteins. We show that @entity32656 specifically binds and methylates @entity1835 at @entity534 -94 and @entity534 -96, both of which comprise the Akt consensus phosphorylation motif. Consistent with the hypothesis, @entity32656 -mediated methylation of these two @entity369 residues inhibits Akt-mediated phosphorylation of @entity1835 at Ser-99 in vitro and in vivo. We also demonstrate that the complex formation of @entity1835 with 14-3-3 proteins, which occurs subsequent to Akt-mediated phosphorylation, is negatively regulated by @entity32656 . Furthermore, @entity32656 knockdown prevents mitochondrial localization of @entity1835 and its binding to the antiapoptotic @entity1836 protein. @entity1835 overexpression causes an increase in apoptosis with concomitant activation of @entity522 , whereas @entity32656 knockdown significantly suppresses these apoptotic processes. Taken together, our results add a new dimension to the complexity of posttranslational @entity1835 regulation and provide evidence that @entity369 methylation within an Akt consensus phosphorylation motif functions as an inhibitory modification against Akt-dependent survival signaling.
