Protein phosphatase 2A negatively regulates eukaryotic initiation factor 4E phosphorylation and eIF4F assembly through direct dephosphorylation of Mnk and eIF4E.

ABSTRACT: The eukaryotic translation initiation factor 4E (eIF4E) is frequently overexpressed in human cancers and is associated with cellular transformation, tumorigenesis, and metastatic progression. It is known that Mnks can phosphorylate eIF4E. Protein phosphatase 2A (PP2A) functions as a tumor suppressor, and it was previously suggested to regulate eIF4E phosphorylation. However, how PP2A regulates eIF4E phosphorylation has not been fully addressed. In this study, we have not only validated the role of PP2A in regulation of eIF4E phosphorylation but also demonstrated the mechanism underlying this process. Inhibition of PP2A using either okadaic acid or PP2A small interfering RNA (siRNA) increased eIF4E phosphorylation, which could be abolished by the presence of the Mnk inhibitor CGP57380 or de

SUBMITTER: Li Y 

PROVIDER: S-EPMC2950334 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature