ArticleThe Journal of experimental medicine2023
P38 kinases mediate NLRP1 inflammasome activation after ribotoxic stress response and virus infection.
Article in The Journal of experimental medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 102 citations in OpenAlex.
- Comparative insights into the apoptosome, inflammasomes and PIDDosome.Nature reviews. Immunology · 2026Review
- Reverse genetics in humanized mice reveals CARD8-mediated pyroptosis causing pancytopenia in human DPP9 deficiency.The Journal of clinical investigation · 2026Article
- Mechanisms and therapeutic opportunities of the ribotoxic stress response in cancer.Molecular oncology · 2026Review
- Protein Post-Translational Modifications in UV-Induced Skin Damage.Experimental dermatology · 2026Review
- Induced pluripotent stem cell-derived macrophages enable broad modeling of human inflammasome signaling.Cell reports methods · 2026Article
- Reverse genetics in humanized mice reveals CARD8-mediated pyroptosis causing pancytopenia in human DPP9 deficiency.bioRxiv : the preprint server for biology · 2026Article
- NLRP1 inflammasome activation in skin equivalents reveals mechanistic insights into the roles of keratinocytes in psoriasis.Cell death & disease · 2026Article
- NLR Inflammasomes in Viral Infections: From Molecular Mechanisms to Therapeutic Interventions.Viruses · 2026Review
- An overview of human inflammasomes: Activation and regulation.Journal of immunology (Baltimore, Md. : 1950) · 2026Review
- When Infection Meets Inflammation:Biology · 2026Review
- Sensing of double-stranded RNA in human cells: molecular mechanisms and cellular consequences.Biochemical Society transactions · 2026Review
- Poxvirus dsDNA genomes differentially activate AIM2 or NLRP3 inflammasomes in human primary cells.The EMBO journal · 2026Article
- A MIF-p38-GSDMD inflammatory loop in keratinocytes underlies UVB-induced cutaneous lupus.Cell death & disease · 2026Article
- Antiviral Inflammasomes and How to Find Them.Viruses · 2026Review
- TAK1 integrates the NLRP1 inflammasome into the innate immune response to double-stranded RNA.bioRxiv : the preprint server for biology · 2026Article
- Redefining Shiga toxin-induced human cell death as NLRP1- and gasdermin E-mediated pyroptosis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Innate immune sensing of alphavirus chikungunya: balancing antiviral defense and pathogenesis.Frontiers in immunology · 2026Review
- Review
- Molecular Evolution of the NLR Gene Family Reveals Diverse Innate Immune Strategies in Bats.Biomolecules · 2025Article
- A selective RPL15 PROTAC degrader enhances anti-PD-1 immunotherapy in a murine melanoma tumor model.Oncogene · 2025Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inflammasomes integrate cytosolic evidence of infection or damage to mount inflammatory responses. The inflammasome sensor NLRP1 is expressed in human keratinocytes and coordinates inflammation in the skin. We found that diverse stress signals induce human NLRP1 inflammasome assembly by activating MAP kinase p38: While the ribotoxic stress response to UV and microbial molecules exclusively activates p38 through MAP3K ZAKα, infection with arthropod-borne alphaviruses, including Semliki Forest and Chikungunya virus, activates p38 through ZAKα and potentially other MAP3K. We demonstrate that p38 directly phosphorylates NLRP1 and that serine 107 in the linker region is critical for activation. NLRP1 phosphorylation is followed by ubiquitination of NLRP1PYD, N-terminal degradation of NLRP1, and nucleation of inflammasomes by NLRP1UPA-CARD. In contrast, activation of NLRP1 by nanobody-mediated ubiquitination, viral proteases, or inhibition of DPP9 was independent of p38 activity. Taken together, we define p38 activation as a unifying signaling hub that controls NLRP1 inflammasome activation by integrating a variety of cellular stress signals relevant to the skin.
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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.