ArticleCell death & disease2010
CLIMP-63 is a gentamicin-binding protein that is involved in drug-induced cytotoxicity.
Article in Cell death & disease, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 39 citations in OpenAlex.
- Palmitoylation in Renal Physiology and Pathology.Biomolecules · 2026Review
- Post-translational protein S-palmitoylation in renal tubular injury: mechanisms and therapeutic implications.Frontiers in cell and developmental biology · 2026Review
- Mechanisms and Impact of Aminoglycoside-Induced Vestibular Deficits.American journal of audiology · 2023Review
- A network map of cytoskeleton-associated protein 4 (CKAP4) mediated signaling pathway in cancer.Journal of cell communication and signaling · 2023Article
- Mitochondrial redox system: A key target of antioxidant therapy to prevent acquired sensorineural hearing loss.Frontiers in pharmacology · 2023Review
- RIPOR2-mediated autophagy dysfunction is critical for aminoglycoside-induced hearing loss.Developmental cell · 2022Article
- Mechanisms of Ototoxicity and Otoprotection.Otolaryngologic clinics of North America · 2021Review
- Mechanisms of Aminoglycoside- and Cisplatin-Induced Ototoxicity.American journal of audiology · 2021Review
- Cytoskeleton-Associated Protein 4, a Promising Biomarker for Tumor Diagnosis and Therapy.Frontiers in molecular biosciences · 2020Review
- Aminoglycoside- and Cisplatin-Induced Ototoxicity: Mechanisms and Otoprotective Strategies.Cold Spring Harbor perspectives in medicine · 2019Review
- CKAP4 Regulates Cell Migration via the Interaction with and Recycling of Integrin.Molecular and cellular biology · 2019Article
- Adverse outcome pathway for aminoglycoside ototoxicity in drug-resistant tuberculosis treatment.Archives of toxicology · 2019Article
- The binding landscape of a partially-selective isopeptidase inhibitor with potent pro-death activity, based on the bis(arylidene)cyclohexanone scaffold.Cell death & disease · 2018Article
- Phenotypic Optimization of Urea-Thiophene Carboxamides To Yield Potent, Well Tolerated, and Orally Active Protective Agents against Aminoglycoside-Induced Hearing Loss.Journal of medicinal chemistry · 2018Article
- Fluorescent aminoglycosides reveal intracellular trafficking routes in mechanosensory hair cells.The Journal of clinical investigation · 2017Article
- Dynamic Editome of Zebrafish under Aminoglycosides Treatment and Its Potential Involvement in Ototoxicity.Frontiers in pharmacology · 2017Article
- Aminoglycoside-Induced Cochleotoxicity: A Review.Frontiers in cellular neuroscience · 2017Review
- Effects of Aminoglycoside Antibiotics on Human Embryonic Stem Cell Viability during Differentiation In Vitro.Stem cells international · 2017Article
- How many lives does CLIMP-63 have?Biochemical Society transactions · 2015Review
- Uptake of fluorescent gentamicin by peripheral vestibular cells after systemic administration.PloS one · 2015Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Aminoglycoside-induced nephrotoxicity and ototoxicity is a major clinical problem. To understand how aminoglycosides, including gentamicin, induce cytotoxicity in the kidney proximal tubule and the inner ear, we identified gentamicin-binding proteins (GBPs) from mouse kidney cells by pulling down GBPs with gentamicin-agarose conjugates and mass spectrometric analysis. Among several GBPs specific to kidney proximal tubule cells, cytoskeleton-linking membrane protein of 63 kDa (CLIMP-63) was the only protein localized in the endoplasmic reticulum, and was co-localized with gentamicin-Texas Red (GTTR) conjugate after cells were treated with GTTR for 1 h. In western blots, kidney proximal tubule cells and cochlear cells, but not kidney distal tubule cells, exhibited a dithiothreitol (DTT)-resistant dimer band of CLIMP-63. Gentamicin treatment increased the presence of DTT-resistant CLIMP-63 dimers in both kidney proximal (KPT11) and distal (KDT3) tubule cells. Transfection of wild-type and mutant CLIMP-63 into 293T cells showed that the gentamicin-dependent dimerization requires CLIMP-63 palmitoylation. CLIMP-63 siRNA transfection enhanced cellular resistance to gentamicin-induced toxicity, which involves apoptosis, in KPT11 cells. Thus, the dimerization of CLIMP-63 is likely an early step in aminoglycoside-induced cytotoxicity in the kidney and cochlea. Gentamicin also enhanced the binding between CLIMP-63 and 14-3-3 proteins, and we also identified that 14-3-3 proteins are involved in gentamicin-induced cytotoxicity, likely by binding to CLIMP-63.
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Registered trials
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