FK506 Binding Protein Mediates Glioma Cell Growth and Sensitivity to Rapamycin Treatment by Regulating NF-κB Signaling Pathway
Open accessAbstract
FK506 binding protein 5 (FKBP5) belongs to a family of immunophilins named for their ability to bind immunosuppressive drugs, also known as peptidyl-prolyl cis-trans isomerases, and also with chaperones to help protein folding. Using glioma cDNA microarray analysis, we found that FKBP5 was overexpressed in glioma tumors. This finding was further validated by real-time reverse transcription-polymerase chain reaction and Western blot analysis. The roles of FKBP5 in glioma cells were then examined. We found that cell growth was suppressed after FKBP5 expression was inhibited by short interfering RNA transfection and enhanced by FKBP5 overexpression. Electrophoretic mobility shift assay showed that nuclear factor-kappa B (NF-kappaB) and DNA binding was enhanced by FKBP5 overexpression. The expression level of I-kappa B alpha and phosphorylated NF-kappaB was regulated by the expression of FKBP5. These data suggest that FKBP5 is involved in NF-kappaB pathway activation in glioma cells. In addition, FKBP5 overexpression in rapamycin-sensitive U87 cells blocked the cells' response to rapamycin treatment, whereas rapamycin-resistant glioma cells, both PTEN-positive and -negative, were synergistically sensitive to rapamycin after FKBP5 was knocked down, suggesting that the FKBP5 regulates glioma cell response to rapamycin treatment. In conclusion, our study demonstrates that FKBP5 plays an important role in glioma growth and chemoresistance through regulating signal transduction of the NF-kappaB pathway.
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Evidence has been provided for a modulation of NF-kB-dependent gene expression by FKBP51, with possible implications for various pathways.
“Evidence has also been provided for a modulation of NF-kB-dependent gene expression by FKBP51, with possible implications for various pathways [79, 80].”
From FKBP51 and FKBP52 in signaling and disease (2011) · cites this paper as [79]
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“Importantly, this double mutation does not alter the FKBP5 interaction with progesterone receptor or HSP90 [22].”
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FKBP51 and FKBP52 in signaling and disease
Storer, C. L., Dickey, C. A., Galigniana, M. D., Rein, T., & Cox, M. B. (2011) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2011.08.001 · Cited by 266 · see citing works
Large FK506-binding proteins shape the pharmacology of rapamycin
März, A. M., Fabian, A.-K., Kozany, C., Bracher, A., & Hausch, F. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.00678-12 · Cited by 141 · see citing works
Stress-responsive FKBP51 regulates AKT2-AS160 signaling and metabolic function
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“, 2003) and NF-kB signaling pathways (Avellino et al., 2005; Jiang et al., 2008; Romano et al., 2004), over-activity of which correlates with several non-PCa malignancies.”
BackgroundThe prospect of FKBP51 as a drug target
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FKBP51 and FKBP52 regulate androgen receptor dimerization and proliferation in prostate cancer cells
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RNAi-Mediated Downregulation of FKBP14 Suppresses the Growth of Human Ovarian Cancer Cells
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- Authors
- Jiang, W., Cazacu, S., Xiang, C., Zenklusen, J. C., Fine, H. A., Berens, M., Armstrong, B., Brodie, C., & Mikkelsen, T.
- Affiliations
- Henry Ford Hospital (US)
- National Institutes of Health (US)
- Translational Genomics Research Institute (US)
- Corresponding author
- Mikkelsen, Tom
- ORCID
- Venue
- Neoplasia
- Publisher
- Elsevier BV
- Published
- 2008-03
- Volume
- 10
- Issue
- 3
- Pages
- 235-243
- ISSN
- 1476-5586 (ISSN-L)
- PMC
- PMC2259453
- OpenAlex
- W1797946869
- Cited by
- 88
- References
- 4
- Citations by year
- 2026: 5 · 2025: 1 · 2024: 2 · 2023: 8 · 2022: 1 · 2021: 5 · 2020: 4 · 2019: 9 · 2018: 1 · 2017: 7 · 2016: 5 · 2015: 9 · 2014: 5 · 2013: 6 · 2012: 1
- FWCI
- 2.61
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Neoplasia (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health
- National Cancer Institute (CA095809, R24CA095809)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- FKBP5, immunophilins, glioma, NF-κB signaling, rapamycin, chemoresistance, cell growth, IκBα phosphorylation, PTEN, U87 cells, peptidyl-prolyl isomerase
- MeSH terms
- Tacrolimus Binding Protein 5, Antibiotics, Antineoplastic, Brain Neoplasms, Glioma, Humans, Signal Transduction, NF-kappa B, Apoptosis, Drug Resistance, Neoplasm, Sirolimus, Oligonucleotide Array Sequence Analysis, Tacrolimus Binding Proteins, Cell Line, Tumor
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