ArticleThe Journal of biological chemistry2011
Importin β1 protein-mediated nuclear localization of death receptor 5 (DR5) limits DR5/tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced cell death of human tumor cells.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 84 citations in OpenAlex.
- Endoplasmic reticulum stress regulates apoptosis and chemotherapeutic via enhancing TNFRSF10B recycling to the cell membrane in triple-negative breast cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- Combination of multivalent DR5 receptor clustering agonists and histone deacetylase inhibitors for treatment of colon cancer.Journal of controlled release : official journal of the Controlled Release Society · 2024Article
- Review
- Stabilization of KPNB1 by deubiquitinase USP7 promotes glioblastoma progression through the YBX1-NLGN3 axis.Journal of experimental & clinical cancer research : CR · 2024Article
- Death receptor 5 promotes tumor progression in gastric cancer.FEBS open bio · 2023Article
- TRAIL Receptor Targeting Agents Potentiate PARP Inhibitor Efficacy in Pancreatic Cancer Independently ofCancers · 2022Article
- TRAIL-receptor 2-a novel negative regulator of p53.Cell death & disease · 2021Article
- Cytotoxic Efficacy and Resistance Mechanism of a TRAIL and VEGFA-Peptide Fusion Protein in Colorectal Cancer Models.International journal of molecular sciences · 2021Article
- Death Receptors DR4 and DR5 Undergo Spontaneous and Ligand-Mediated Endocytosis and Recycling Regardless of the Sensitivity of Cancer Cells to TRAIL.Frontiers in cell and developmental biology · 2021Article
- YIPF2 promotes chemotherapeutic agent-mediated apoptosis via enhancing TNFRSF10B recycling to plasma membrane in non-small cell lung cancer cells.Cell death & disease · 2020Article
- Death Receptor 5 Displayed on Extracellular Vesicles Decreases TRAIL Sensitivity of Colon Cancer Cells.Frontiers in cell and developmental biology · 2020Article
- TRAIL Induces Nuclear Translocation and Chromatin Localization of TRAIL Death Receptors.Cancers · 2019Article
- Heterogeneous intracellular TRAIL-receptor distribution predicts poor outcome in breast cancer patients.Journal of molecular medicine (Berlin, Germany) · 2019Article
- Natural Product Mediated Regulation of Death Receptors and Intracellular Machinery: Fresh from the Pipeline about TRAIL-Mediated Signaling and Natural TRAIL Sensitizers.International journal of molecular sciences · 2019Review
- GSTM1 polymorphism in Oncotype DX assay is a potential predictive factor for taxane-based neoadjuvant chemotherapy in estrogen receptor-positive Chinese breast cancer patients.Translational cancer research · 2019Article
- Targeting KPNB1 overcomes TRAIL resistance by regulating DR5, Mcl-1 and FLIP in glioblastoma cells.Cell death & disease · 2019Article
- Tumor necrosis factor-related apoptosis-inducing ligand inhibits the growth and aggressiveness of colon carcinoma via the exogenous apoptosis signaling pathway.Experimental and therapeutic medicine · 2019Article
- TRAIL-Receptor 4 Modulates γδ T Cell-Cytotoxicity Toward Cancer Cells.Frontiers in immunology · 2019Article
- Developing TRAIL/TRAIL death receptor-based cancer therapies.Cancer metastasis reviews · 2018Review
- Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/death receptor 5 (DR5)-mediated cell death plays an important role in the elimination of tumor cells and transformed cells. Recently, recombinant TRAIL and agonistic anti-DR5 monoclonal antibodies have been developed and applied to cancer therapy. However, depending on the type of cancer, the sensitivity to TRAIL has been reportedly different, and some tumor cells are resistant to TRAIL-mediated apoptosis. Using confocal microscopy, we found that large amounts of DR5 were localized in the nucleus in HeLa and HepG2 cells. Moreover, these tumor cells were resistant to TRAIL, whereas DU145 cells, which do not have nuclear DR5, were highly sensitive to TRAIL. By means of immunoprecipitation and Western blot analysis, we found that DR5 and importin β1 were physically associated, suggesting that the nuclear DR5 was transported through the nuclear import pathway mediated by importin β1. Two functional nuclear localization signals were identified in DR5, the mutation of which abrogated the nuclear localization of DR5 in HeLa cells. Moreover, the nuclear transport of DR5 was also prevented by the knockdown of importin β1 using siRNA, resulting in the up-regulation of DR5 expression on the cell surface and an increased sensitivity of HeLa and HepG2 cells to TRAIL. Taken together, our findings suggest that the importin β1-mediated nuclear localization of DR5 limits the DR5/TRAIL-induced cell death of human tumor cells and thus can be a novel target to improve cancer therapy with recombinant TRAIL and anti-DR5 antibodies.
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