Akt-Mediated Phosphorylation of Argonaute 2 Downregulates Cleavage and Upregulates Translational Repression of MicroRNA Targets
0301 basic medicine
0303 health sciences
Down-Regulation
Cell Biology
Proto-Oncogene Mas
Cell Line
Up-Regulation
MicroRNAs
03 medical and health sciences
HEK293 Cells
Cell Line, Tumor
Argonaute Proteins
Humans
Phosphorylation
Molecular Biology
Proto-Oncogene Proteins c-akt
HeLa Cells
DOI:
10.1016/j.molcel.2013.03.015
Publication Date:
2013-04-18T16:38:59Z
AUTHORS (14)
ABSTRACT
A high-throughput RNA interference (RNAi) screen targeting 542 genes of the human kinome was used to discover regulators of RNAi. Here we report that the proto-oncogene Akt-3/PKBγ (Akt3) phosphorylates Argonaute 2 (Ago2) at S387, which downregulates cleavage and upregulates translational repression of endogenous microRNA (miRNA)-targeted messenger RNAs (mRNAs). We further demonstrate that Akt3 coimmunoprecipitates with Ago2 and phosphorylation of Ago2 at S387 facilitates its interaction with GW182 and localization to cytoplasmic processing bodies (P bodies), where miRNA-targeted mRNAs are thought to be stored and degraded. Therefore, Akt3-mediated phosphorylation of Ago2 is a molecular switch between target mRNA cleavage and translational repression activities of Ago2.
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