ArticleCancer letters2015
Tyrosine phosphorylation of HSC70 and its interaction with RFC mediates methotrexate resistance in murine L1210 leukemia cells.
Article in Cancer letters, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 16 citations in OpenAlex.
- Starvation-induced HSC70 O-GlcNAcylation activates chaperone-mediated autophagy.The Journal of biological chemistry · 2026Article
- Targeting chaperone modifications: Innovative approaches to cancer treatment.The Journal of biological chemistry · 2024Review
- Unveiling the Therapeutic Potential of Folate-Dependent One-Carbon Metabolism in Cancer and Neurodegeneration.International journal of molecular sciences · 2024Review
- Review
- Association of anti-HSC70 autoantibodies with cutaneous ulceration and severe disease in juvenile dermatomyositis.Rheumatology (Oxford, England) · 2022Article
- Post-translational modifications of Hsp70 family proteins: Expanding the chaperone code.The Journal of biological chemistry · 2020Review
- Identification of GdRFC1 as a novel regulator of telomerase in Giardia duodenalis.Parasitology research · 2020Article
- Quantitative Tyrosine Phosphoproteomic Analysis of Resistance to Radiotherapy in Nasopharyngeal Carcinoma Cells.Cancer management and research · 2020Article
- Heat Shock Proteins: Agents of Cancer Development and Therapeutic Targets in Anti-Cancer Therapy.Cells · 2019Review
- DNLC: differential network local consistency analysis.BMC bioinformatics · 2019Article
- Selective Autophagy Regulates Cell Cycle in Cancer Therapy.Theranostics · 2019Review
- Genistein suppresses aerobic glycolysis and induces hepatocellular carcinoma cell death.British journal of cancer · 2017Article
- Doxorubicin induces apoptosis by targeting Madcam1 and AKT and inhibiting protein translation initiation in hepatocellular carcinoma cells.Oncotarget · 2015Article
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
We previously identified and characterized a 66-68 kDa membrane-associated, tyrosine phosphorylated protein in murine leukemia L1210 cells as HSC70 which is a methotrexate (MTX)-binding protein. In order to further characterize the functional role of HSC70 in regulating MTX resistance in L1210 cells, we first showed that HSC70 colocalizes and interacts with reduced folate carrier (RFC) in L1210 cells by confocal laser scanning microscopy and Duolink in situ proximity ligation assay. The tyrosine phosphorylation status of HSC70 found in the membrane fraction was different from the parental L1210/0 and cisplatin (CDDP)-MTX cross resistant L1210/DDP cells. In MTX-binding assays, HSC70 from L1210/DDP cells showed less affinity for MTX-agarose beads than that of L1210/0 cells. In addition, genistein (a tyrosine phosphorylation inhibitor) significantly enhanced the resistance of L1210/0 cells to MTX. Moreover, site-directed mutation studies indicated the importance of tyrosine phosphorylation of HSC70 in regulating its binding to MTX. These findings suggest that tyrosine phosphorylation of HSC70 regulates the transportation of MTX into the cells via the HSC70-RFC system and contributes to MTX resistance in L1210 cells.
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