ArticleThe Journal of biological chemistry2020
Human polymorphisms in GSDMD alter the inflammatory response.
Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- The dysfunction of complement and coagulation in diseases: the implications for the therapeutic interventions.MedComm · 2024Review
- Nickel Induces Pyroptosis via the Nrf2/NLRP3 Pathway in Kidney of Mice.Biological trace element research · 2024Article
- Post-translational control of NLRP3 inflammasome signaling.The Journal of biological chemistry · 2024Review
- Pyroptosis in health and disease.American journal of physiology. Cell physiology · 2024Review
- Review
- Article
- Gasdermins gone wild: new roles for GSDMs in regulating cellular homeostasis.Trends in cell biology · 2023Review
- Genetic characterization of Macaca arctoides: A highlight of key genes and pathways.Primates; journal of primatology · 2023Article
- Gasdermin D kills bacteria.Microbiological research · 2023Review
- Characterization of GSDME in amphioxus provides insights into the functional evolution of GSDM-mediated pyroptosis.PLoS biology · 2023Article
- Zika virus cleaves GSDMD to disseminate prognosticable and controllable oncolysis in a human glioblastoma cell model.Molecular therapy oncolytics · 2023Article
- Regulation of gasdermins in pyroptosis and cytokine release.Advances in immunology · 2023Article
- Transcriptomic and proteomic retinal pigment epithelium signatures of age-related macular degeneration.Nature communications · 2022Article
- Chemical Modulation of Gasdermin-Mediated Pyroptosis and Therapeutic Potential.Journal of molecular biology · 2022Review
- E3 ubiquitin ligase SYVN1 is a key positive regulator for GSDMD-mediated pyroptosis.Cell death & disease · 2022Article
- Gasdermins in Innate Host Defense AgainstFrontiers in immunology · 2022Review
- Screening of crosstalk and pyroptosis-related genes linking periodontitis and osteoporosis based on bioinformatics and machine learning.Frontiers in immunology · 2022Article
- Emerging mechanisms of immunocoagulation in sepsis and septic shock.Trends in immunology · 2021Review
- Channelling inflammation: gasdermins in physiology and disease.Nature reviews. Drug discovery · 2021Review
- Discovery of a caspase cleavage motif antibody reveals insights into noncanonical inflammasome function.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Exomic studies have demonstrated that innate immune genes exhibit an even higher degree of variation than the majority of other gene families. However, the phenotypic implications of this genetic variation are not well understood, with effects ranging from hypomorphic to silent to hyperfunctioning. In this work, we study the functional consequences of this variation by investigating polymorphisms in gasdermin D, the key pyroptotic effector protein. We find that, although SNPs affecting potential posttranslational modifications did not affect gasdermin D function or pyroptosis, polymorphisms disrupting sites predicted to be structurally important dramatically alter gasdermin D function. The manner in which these polymorphisms alter function varies from conserving normal pyroptotic function to inhibiting caspase cleavage to disrupting oligomerization and pore formation. Further, downstream of inflammasome activation, polymorphisms that cause loss of gasdermin D function convert inflammatory pyroptotic cell death into immunologically silent apoptotic cell death. These findings suggest that human genetic variation can alter mechanisms of cell death in inflammation.
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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.