Fine-tuning AKT kinase activity through direct lysine methylation

This is the authors' abstract. We don't add key points for this paper.

In addition to the pivotal roles for histone methylation in the transcriptional regulation, emerging evidence suggests important roles for methylation of non-histone proteins in response to extra-cellular stimulatory events, with implications in governing tumorigenesis. Among the increasing list of non-histone proteins targeted for methylation, the tri-lysine-methylation modification of AKT has been recently identified to fine-tune its kinase activity and oncogenic functions. Moreover, our results implicate the histone methyltransferase SETDB1 as the methyltransferase modifying and activating AKT in a PI3K dependent manner. As such, the oncogenic function of SETDB1 in various cancers may be attributed to tumorigenesis, at least in part, through activating AKT. Therefore, targeting SETDB1, which modulates both epigenetic marks and AKT kinase activity simultaneously, is a potential strategy for novel cancer therapeutics.