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FKBP51 Affects Cancer Cell Response to Chemotherapy by Negatively Regulating Akt
Open accessAbstract
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.
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“FKBP51 expression is decreased in several cancer cell lines and in pancreatic cancer tissue, and may correlate with increased Akt phosphorylation and reduced cell sensitivity to chemotherapeutic agents.”
From FKBP51 and FKBP52 in signaling and disease (2011) · cites this paper as [50]
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“A major advance in mechanistic understanding was the discovery that FKBP51 negatively regulates the activity of the cell growth regulator Akt, by serving as a scaffolding protein to recruit the phosphatase PHLPP [50].”
From FKBP51 and FKBP52 in signaling and disease (2011) · cites this paper as [50]
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“FKBP51 and FKBP52 likely have a similar activity; however, unlike Pin1, the FKBPs likely coordinate with Hsp90 to isomerize tau [50].”
From FKBP51 and FKBP52 in signaling and disease (2011) · cites this paper as [50]
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Cites
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Cell Autonomous Role of PTEN in Regulating Castration-Resistant Prostate Cancer Growth
Mulholland, D. J., Tran, L. M., Li, Y., Cai, H., Morim, A., Wang, S., Plaisier, S. B., Garraway, I. P., Huang, J., Graeber, T. G., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.05.006 · Cited by 533
Metadata
- Authors
- Pei, H., Li, L., Fridley, B. L., Jenkins, G. D., Kalari, K. R., Lingle, W., Petersen, G., Lou, Z., & Wang, L.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Lou, Zhenkun
- Wang, Liewei
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2009-09
- Volume
- 16
- Issue
- 3
- Pages
- 259-266
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC2755578
- OpenAlex
- W1996667997
- Cited by
- 709
- References
- 27
- Citations by year
- 2026: 23 · 2025: 26 · 2024: 31 · 2023: 44 · 2022: 59 · 2021: 73 · 2020: 63 · 2019: 53 · 2018: 39 · 2017: 48 · 2016: 43 · 2015: 47 · 2014: 48 · 2013: 37 · 2012: 24
- FWCI
- 9.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (CA102701, P20CA102701, K22CA130828, P50CA102701, R01CA130996, R01CA129344, R01CA138461)
- National Institute of General Medical Sciences (U01GM061388, U19GM061388, GM61388)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- FKBP51, Akt, PHLPP, Akt dephosphorylation, scaffold proteins, pancreatic cancer, chemotherapy response, genotoxic stress, cell death
- MeSH terms
- Docetaxel, Tacrolimus Binding Protein 5, Antimetabolites, Antineoplastic, Antineoplastic Agents, Antineoplastic Agents, Phytogenic, Cell Line, Cytarabine, Drug Therapy, Humans, Kidney, Neoplasms, Nuclear Proteins, Pancreatic Neoplasms, Phosphoprotein Phosphatases, Paclitaxel, Tacrolimus Binding Proteins, Taxoids, Cell Line, Tumor, Proto-Oncogene Proteins c-akt
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