FKBP51 Affects Cancer Cell Response to Chemotherapy by Negatively Regulating Akt

By Huadong Pei, Liang Li, B. Fridley, G. Jenkins, Krishna Rani Kalari, W. Lingle, G. Petersen, Zhenkun Lou, Liewei Wang. Cancer Cell, 2009

704 citations recorded by the source corpus.

SUMMARY 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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/fa8e8d83afb876f6897cdb9441a9570a3050c7ea

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Citations in the corpus

• Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer. (2011, background): “The immunophilin FKBP5 is a chaperone for the AKT phosphatase PHLPP, and its expression in prostate cancer is androgen dependent (Gao et al., 2005; Pei et al., 2009).”
• Subtypes of Pancreatic Ductal Adenocarcinoma and Their Differing Responses to Therapy (2011, background): “Analysis of PDAssigner gene expression in three additional published PDA expression data sets of unique origin, platform or processin”