ArticleCell death & disease2018
GRP75 modulates oncogenic Dbl-driven endocytosis derailed via the CHIP-mediated ubiquitin degradation pathway.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Biomarkers of tumor invasiveness in proteomics (Review).International journal of oncology · 2020Pooled it
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- Lysophosphatidic acid-induced Arf6-driven macropinocytosis of CD147International journal of biological sciences · 2026Article
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- BI1 Activates Autophagy and Mediates TDP43 to Regulate ALS Pathogenesis.Molecular neurobiology · 2025Article
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- Vesicle-mediated transport-related genes predict the prognosis and immune microenvironment in hepatocellular carcinoma.Journal of Cancer · 2024Article
- Chaperone-assisted E3 ligase CHIP: A double agent in cancer.Genes & diseases · 2022Review
- GRP75-driven, cell-cycle-dependent macropinocytosis of Tat/pDNA-CaJournal of nanobiotechnology · 2022Article
- GRP75-faciliated Mitochondria-associated ER Membrane (MAM) Integrity controls Cisplatin-resistance in Ovarian Cancer Patients.International journal of biological sciences · 2022Article
- Insights Into the Role of Mortalin in Alzheimer's Disease, Parkinson's Disease, and HIV-1-Associated Neurocognitive Disorders.Frontiers in cell and developmental biology · 2022Review
- Arf6-driven endocytic recycling of CD147 determines HCC malignant phenotypes.Journal of experimental & clinical cancer research : CR · 2019Article
- YIPF2 is a novel Rab-GDF that enhances HCC malignant phenotypes by facilitating CD147 endocytic recycle.Cell death & disease · 2019Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chaperone-assisted proteasome degradation of oncogenic protein acts as an upstream signal controlling tumorigenesis and progression. The understanding of the co-regulation of chaperone and oncoprotein of endocytosis pathways is extremely limited. In this study, we showed for the first time that proto-Dbl (dbl proto-oncogene product) is co-enriched with mitochondrial chaperone GRP75 in endocytosis vesicles from ovarian cancer cells. onco-Dbl, produced by oncogenic mutation/degradation of proto-Dbl, markedly enhanced cellular macropinocytosis but suppressed clathrin-mediated endocytosis and clathrin-independent endocytosis pathways, presenting a derailed endocytosis phenotype. GRP75 was associated with proto-Dbl inside cells and modulated Dbl-driven endocytosis derailed by a co-regulatory mode. In spite of not being a component of the Hsc70/Hsp90/proto-Dbl complex, the degradation of proto-Dbl was promoted by GRP75 through the CHIP-mediated ubiquitin-proteasome pathway, of which GRP75 acts as a cooperator with CHIP but also acts as a competitor to Hsc70 and Hsp90 in the multiple chaperones-assisted pro-folding/pro-degradation machinery. Knockdown or inhibition of GRP75 attenuated proto-Dbl degradation and reduced the onco-Dbl level, which differentially impaired Rho GTPases activation and therefore shifted the endocytosis-derailed phenotype. Our data uncovered a novel GRP75-Dbl endocytosis regulatory axis and provided an alternative using chaperone inhibitor to shut down the oncoprotein-driven endocytosis derailment mechanism.
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