ArticleCell cycle (Georgetown, Tex.)2008
Proteasome inhibitors increase tubulin polymerization and stabilization in tissue culture cells: a possible mechanism contributing to peripheral neuropathy and cellular toxicity following proteasome inhibition.
Article in Cell cycle (Georgetown, Tex.), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 110 citations in OpenAlex.
- Trial
- Characterization of Alternaria alternata alternariol monomethyl ether with a potential antiproliferative activity by topoisomerases inhibition; molecular docking and dynamic simulations.Scientific reports · 2026Article
- Preventing neuropathy and improving anticancer chemotherapy with a carbazole-based compound.Science advances · 2025Article
- Functional Characterization of Pathway Inhibitors for the Ubiquitin-Proteasome System (UPS) as Tool Compounds for CRBN and VHL-Mediated Targeted Protein Degradation.ACS chemical biology · 2025Article
- Degradation bottlenecks and resource competition in transiently and stably engineered mammalian cells.Nature communications · 2025Article
- Bortezomib-induced peripheral neuropathy: from molecular mechanisms to clinical management.Frontiers in pharmacology · 2025Review
- The nociceptive activity of peripheral sensory neurons is modulated by the neuronal membrane proteasome.Cell reports · 2024Article
- Bortezomib Is Toxic but Induces Neurogenesis and Inhibits TUBB3 Degradation in Rat Neural Stem Cells.Biomolecules & therapeutics · 2024Article
- Current understanding of the molecular mechanisms of chemotherapy-induced peripheral neuropathy.Frontiers in molecular neuroscience · 2024Review
- Ozone in Chemotherapy-Induced Peripheral Neuropathy-Current State of Art, Possibilities, and Perspectives.International journal of molecular sciences · 2023Review
- Review
- Specific Attenuation of Purinergic Signaling during Bortezomib-Induced Peripheral Neuropathy In Vitro.International journal of molecular sciences · 2022Article
- Mechanisms of Chemotherapy-Induced Neurotoxicity.Frontiers in pharmacology · 2022Review
- Chemotherapy-Induced Peripheral Neuropathy: Mechanisms and Therapeutic Avenues.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Review
- Tubulin binding potentially clears up Bortezomib and Carfilzomib differential neurotoxic effect.Scientific reports · 2021Article
- Vincristine- and bortezomib-induced neuropathies - from bedside to bench and back.Experimental neurology · 2021Review
- Pathological Mechanisms of Bortezomib-Induced Peripheral Neuropathy.International journal of molecular sciences · 2021Review
- Recent Research Progress of Chiral Small Molecular Antitumor-Targeted Drugs Approved by the FDA From 2011 to 2019.Frontiers in oncology · 2021Review
- Folding for the Immune Synapse: CCT Chaperonin and the Cytoskeleton.Frontiers in cell and developmental biology · 2021Review
- The chaperonin CCT controls T cell receptor-driven 3D configuration of centrioles.Science advances · 2020Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Bortezomib (Velcade((R))), a proteasome inhibitor, is approved by the FDA for the treatment of multiple myeloma (MM). While effective, its use has been hampered by peripheral neurotoxicity of unexplained etiology. Since proteasome inhibitors alter protein degradation, we speculated that proteins regulating microtubule (MT) stability may be affected after treatment and examined MT polymerization in cells by comparing the distribution of tubulin between polymerized (P) and soluble (S) fractions. We observed increased MT polymerization following treatment of SY5Y and KCNR [neuroblastoma], HCN2, and 8226 [MM] cells, using five proteasome inhibitors; the baseline proportion of total alpha-tubulin in 'P' fractions ranged from approximately 41-68%, and increased to approximately 55-99% after treatment. Increased acetylated alpha-tubulin, a post-translational marker of stabilized MTs, was observed in the neural cell lines HCN1A and HCN2 and this was sustained up to 144 hours after the proteasome inhibitor was removed. Cell cycle analysis of three cell lines after treatment, showed approximately 50-75% increases in the G(2)M phase. Immunofluorescent localization studies of proteasome inhibitor treated cells did not reveal microtubule bundles in contrast to paclitaxel treated, suggesting MT stabilization via a mechanism other than direct drug binding. We examined the levels of microtubule associated proteins and observed a 1.4-3.7 fold increase in the microtubule associated protein MAP2, in HCN2 cells following treatment with proteasome inhibitors. These data provide a plausible explanation for the neurotoxicity observed clinically and raise the possibility that microtubule stabilization contributes to cytotoxicity.
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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.