ArticleOncogene2017
FKBP12 enhances sensitivity to chemotherapy-induced cancer cell apoptosis by inhibiting MDM2.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 51 citations in OpenAlex.
- Point-of-Care Tests via Pollen-Based Nanoplasmonic Chips Combined with a Synthetic Receptor for FKBP12 Biomarker Detection at a Single-Molecule Level.ACS applied nano materials · 2025Article
- Combining QCM and SERS on a Nanophotonic Chip: A Dual-Functional Sensor for Biomolecular Interaction Analysis and Protein Fingerprinting.Nanomaterials (Basel, Switzerland) · 2025Article
- The stability of FKBP9 maintained by BiP is crucial for glioma progression.Genes & diseases · 2024Article
- SPI1 activates TGF-β1/PI3K/Akt signaling through transcriptional upregulation of FKBP12 to support the mesenchymal phenotype of glioma stem cells.Brain pathology (Zurich, Switzerland) · 2024Article
- The prognostic and immunological role of FKBP1A in an integrated muti-omics cancers analysis, especially lung cancer.Journal of cancer research and clinical oncology · 2023Article
- S100A6 inhibits MDM2 to suppress breast cancer growth and enhance sensitivity to chemotherapy.Breast cancer research : BCR · 2023Article
- Integrated analysis of FKBP1A/SLC3A2 axis in everolimus inducing ferroptosis of breast cancer and anti-proliferation of T lymphocyte.International journal of medical sciences · 2023Article
- UpregulatedInternational journal of molecular sciences · 2022Article
- The Prognostic Significance ofInternational journal of molecular sciences · 2022Article
- Acetylation, Phosphorylation, Ubiquitination (Oh My!): Following Post-Translational Modifications on the Ubiquitin Road.Biomolecules · 2022Review
- Apoptosis Effects ofGalen medical journal · 2022Article
- Transcriptional epigenetic regulation of Fkbp1/Pax9 genes is associated with impaired sensitivity to platinum treatment in ovarian cancer.Clinical epigenetics · 2021Article
- The roles and regulation of MDM2 and MDMX: it is not just about p53.Genes & development · 2021Review
- High-dose rapamycin exerts a temporary impact on T. reesei RUT-C30 through gene trFKBP12.Biotechnology for biofuels · 2021Article
- E3 Ubiquitin Ligase in Anticancer Drugdsla Resistance: Recent Advances and Future Potential.Frontiers in pharmacology · 2021Review
- FKBP9 promotes the malignant behavior of glioblastoma cells and confers resistance to endoplasmic reticulum stress inducers.Journal of experimental & clinical cancer research : CR · 2020Article
- Knockdown of interferon-stimulated gene 15 affects the sensitivity of hepatocellular carcinoma cells to norcantharidin.Experimental and therapeutic medicine · 2019Article
- FKBP12 is a predictive biomarker for efficacy of anthracycline-based chemotherapy in breast cancer.Cancer chemotherapy and pharmacology · 2019Article
- FKBP12: A partner of Snx10 required for vesicular trafficking in osteoclasts.Journal of cellular biochemistry · 2019Article
- Curcumin induced oxidative stress attenuation by N-acetylcysteine co-treatment: a fibroblast and epithelial cell in-vitro study in idiopathic pulmonary fibrosis.Molecular medicine (Cambridge, Mass.) · 2019Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The FK506-binding protein 12 (FKBP12) is a cytoplasmic protein and has been reported to possess multiple functions in signaling transduction based on its interaction with different cellular targets. Here, we report that FKBP12 interacts with oncoprotein MDM2 and induces MDM2 degradation. We demonstrate that FKBP12 degrades MDM2 through binding to MDM2 protein, disrupting MDM2/MDM4 interaction and inducing MDM2 self-ubiquitination. The FKBP12-mediated MDM2 degradation was significantly enhanced when the transfected MDM2 was localized in the cytoplasm. The endogenous MDM2, when it was induced by p53 subjecting to DNA-damaging stimuli such as treatment with doxorubicin, was also significantly inhibited by FKBP12. This is due to translocation of p53-induced MDM2 from the nucleus to the cytoplasm, which facilitates interaction with cytoplasmic FKBP12. Furthermore, the enhanced level of MDM2 following p53 activation in nutlin-3 treated cells was also inhibited by FKBP12. The FKBP12-mediated downregulation of MDM2 in response to doxorubicin or nutlin-3 results in continuing and constitutive activation of p53, inhibition of XIAP and sensitization of cancer cells to apoptosis. These results identify a novel function for FKBP12 in downregulating MDM2, which directly enhances sensitivity of cancer cells to chemotherapy and nutlin-3 treatment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.