ArticleMolecular biology of the cell2014
A cellular genome-wide association study reveals human variation in microtubule stability and a role in inflammatory cell death.
Article in Molecular biology of the cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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27 citing papers in PubMed, 46 citations in OpenAlex.
- The impact of anti-gout medications on eight cardiovascular diseases: a Mendelian randomized study.European journal of clinical pharmacology · 2026Article
- Human umbilical cord mesenchymal stem cell-derived exosomes prevent and alleviate experimental pulmonary fibrosis by modulating the cytoskeleton of macrophages.Stem cell research & therapy · 2025Article
- Therapeutic Potential of TUBB6 Inhibition for Hematoma Reduction, Microtubule Stabilization, and Neurological Recovery in an In Vivo Model of Intracerebral Hemorrhage.Neuromolecular medicine · 2025Article
- Pyroptosis leads to loss of centrosomal integrity in macrophages.Cell death discovery · 2024Article
- Genetic influence on vascular smooth muscle cell apoptosis.Cell death & disease · 2024Article
- Proteomic and metabolomic characterizations of moyamoya disease patient sera.Brain and behavior · 2023Article
- Dynamics of TUBB protein with five majorly occurring natural variants: a risk of cortical dysplasia.Journal of molecular modeling · 2023Article
- Assessing Cytoskeletal Destruction During Pyroptosis.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Single-cell genome-wide association reveals that a nonsynonymous variant inCell genomics · 2022Article
- A human iPSC-array-based GWAS identifies a virus susceptibility locus in the NDUFA4 gene and functional variants.Cell stem cell · 2022Article
- Pyroptosis-related genes play a significant role in the prognosis of gastric cancer.World journal of clinical cases · 2022Article
- Metabolomic Profiling Reveals Protective Effects and Mechanisms of Sea Buckthorn Sterol against Carbon Tetrachloride-Induced Acute Liver Injury in Rats.Molecules (Basel, Switzerland) · 2022Article
- A Novel Pyroptosis-Related Prognostic Signature for Risk Stratification and Clinical Prognosis in Clear Cell Renal Cell Carcinoma.Disease markers · 2022Article
- Possible Roles of Specific Amino Acids in β-Tubulin Isotypes in the Growth and Maintenance of Neurons: Novel Insights From Cephalopod Mollusks.Frontiers in molecular neuroscience · 2022Article
- Article
- Inflammasome-Induced Osmotic Pressure and the Mechanical Mechanisms Underlying Astrocytic Swelling and Membrane Blebbing in Pyroptosis.Frontiers in immunology · 2021Article
- Modeling of variables in cellular infection reveals CXCL10 levels are regulated by human genetic variation and the Chlamydia-encoded CPAF protease.Scientific reports · 2020Article
- LCM-seq reveals unique transcriptional adaptation mechanisms of resistant neurons and identifies protective pathways in spinal muscular atrophy.Genome research · 2020Article
- The Tubulin Code in Microtubule Dynamics and Information Encoding.Developmental cell · 2020Review
- Persistent upregulation of the β-tubulin tubb6, linked to muscle regeneration, is a source of microtubule disorganization in dystrophic muscle.Human molecular genetics · 2019Article
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6 authors at 2 institutions in 1 country.
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Abstract
Pyroptosis is proinflammatory cell death that occurs in response to certain microbes. Activation of the protease caspase-1 by molecular platforms called inflammasomes is required for pyroptosis. We performed a cellular genome-wide association study (GWAS) using Salmonella typhimurium infection of human lymphoblastoid cell lines as a means of dissecting the genetic architecture of susceptibility to pyroptosis and identifying unknown regulatory mechanisms. Cellular GWAS revealed that a common human genetic difference that regulates pyroptosis also alters microtubule stability. An intergenic single-nucleotide polymorphism on chromosome 18 is associated with decreased pyroptosis and increased expression of TUBB6 (tubulin, β 6 class V). TUBB6 is unique among tubulin isoforms in that its overexpression can completely disrupt the microtubule network. Cells from individuals with higher levels of TUBB6 expression have lower microtubule stability and less pyroptosis. Reducing TUBB6 expression or stabilizing microtubules pharmacologically with paclitaxel (Taxol) increases pyroptosis without affecting the other major readout of caspase-1 activation, interleukin-1β secretion. The results reveal a new role for microtubules and possibly specific tubulin isoforms in the execution of pyroptosis. Furthermore, the finding that there is common diversity in TUBB6 expression and microtubule stability could have broad consequences for other microtubule-dependent phenotypes, diseases, and pharmacological responses.
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