There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.
Abstract
Akt is a central regulator of cell growth. Its activity can be negatively regulated
by the phosphatase PHLPP that specifically dephosphorylates the hydrophobic motif
of Akt (Ser473 in Akt1). However, how PHLPP is targeted to Akt is not clear. Here
we show that FKBP51 (FK506-binding protein 51) acts as a scaffolding protein for Akt
and PHLPP and promotes dephosphorylation of Akt. Furthermore, FKBP51 is downregulated
in pancreatic cancer tissue samples and several cancer cell lines. Decreased FKBP51
expression in cancer cells results in hyperphosphorylation of Akt and decreased cell
death following genotoxic stress. Overall, our findings identify FKBP51 as a negative
regulator of the Akt pathway, with potentially important implications for cancer etiology
and response to chemotherapy.