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ZAKα-driven ribotoxic stress response activates the human NLRP1 inflammasome.
Robinson, Kim S; Toh, Gee Ann; Rozario, Pritisha; Chua, Rae; Bauernfried, Stefan; Sun, Zijin; Firdaus, Muhammad Jasrie; Bayat, Shima; Nadkarni, Rhea; Poh, Zhi Sheng; Tham, Khek Chian; Harapas, Cassandra R; Lim, Chrissie K; Chu, Werncui; Tay, Celest W S; Tan, Kiat Yi; Zhao, Tianyun; Bonnard, Carine; Sobota, Radoslaw; Connolly, John E; Common, John; Masters, Seth L; Chen, Kaiwen W; Ho, Lena; Wu, Bin; Hornung, Veit; Zhong, Franklin L.
Afiliación
  • Robinson KS; Skin Research Institute of Singapore (SRIS), 308232 Singapore.
  • Toh GA; Agency for Science, Technology and Research (A*STAR) Skin Research Laboratories (ASRL), 138648 Singapore.
  • Rozario P; Lee Kong Chian School of Medicine, Nanyang Technological University, 308232 Singapore.
  • Chua R; Lee Kong Chian School of Medicine, Nanyang Technological University, 308232 Singapore.
  • Bauernfried S; Lee Kong Chian School of Medicine, Nanyang Technological University, 308232 Singapore.
  • Sun Z; Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, 81377 Munich, Germany.
  • Firdaus MJ; Max-Planck Institute of Biochemistry, 82152 Martinsried, Germany.
  • Bayat S; Lee Kong Chian School of Medicine, Nanyang Technological University, 308232 Singapore.
  • Nadkarni R; Lee Kong Chian School of Medicine, Nanyang Technological University, 308232 Singapore.
  • Poh ZS; Lee Kong Chian School of Medicine, Nanyang Technological University, 308232 Singapore.
  • Tham KC; Cardiovascular Metabolic Disorders Program, Duke-NUS Medical School, 169857 Singapore.
  • Harapas CR; Lee Kong Chian School of Medicine, Nanyang Technological University, 308232 Singapore.
  • Lim CK; Agency for Science, Technology and Research (A*STAR) Skin Research Laboratories (ASRL), 138648 Singapore.
  • Chu W; Inflammation Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
  • Tay CWS; Institute of Molecular and Cell Biology, A*STAR, 138673 Singapore.
  • Tan KY; Present address: MiroBio Limited, Oxford OX4 4GE, UK.
  • Zhao T; Cardiovascular Metabolic Disorders Program, Duke-NUS Medical School, 169857 Singapore.
  • Bonnard C; Lee Kong Chian School of Medicine, Nanyang Technological University, 308232 Singapore.
  • Sobota R; Agency for Science, Technology and Research (A*STAR) Skin Research Laboratories (ASRL), 138648 Singapore.
  • Connolly JE; Institute of Molecular and Cell Biology, A*STAR, 138673 Singapore.
  • Common J; Skin Research Institute of Singapore (SRIS), 308232 Singapore.
  • Masters SL; Agency for Science, Technology and Research (A*STAR) Skin Research Laboratories (ASRL), 138648 Singapore.
  • Chen KW; Institute of Molecular and Cell Biology, A*STAR, 138673 Singapore.
  • Ho L; Institute of Molecular and Cell Biology, A*STAR, 138673 Singapore.
  • Wu B; Agency for Science, Technology and Research (A*STAR) Skin Research Laboratories (ASRL), 138648 Singapore.
  • Hornung V; Inflammation Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
  • Zhong FL; Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.
Science ; 377(6603): 328-335, 2022 07 15.
Article en En | MEDLINE | ID: mdl-35857590
Human NLRP1 (NACHT, LRR, and PYD domain-containing protein 1) is an innate immune sensor predominantly expressed in the skin and airway epithelium. Here, we report that human NLRP1 senses the ultraviolet B (UVB)- and toxin-induced ribotoxic stress response (RSR). Biochemically, RSR leads to the direct hyperphosphorylation of a human-specific disordered linker region of NLRP1 (NLRP1DR) by MAP3K20/ZAKα kinase and its downstream effector, p38. Mutating a single ZAKα phosphorylation site in NLRP1DR abrogates UVB- and ribotoxin-driven pyroptosis in human keratinocytes. Moreover, fusing NLRP1DR to CARD8, which is insensitive to RSR by itself, creates a minimal inflammasome sensor for UVB and ribotoxins. These results provide insight into UVB sensing by human skin keratinocytes, identify several ribotoxins as NLRP1 agonists, and establish inflammasome-driven pyroptosis as an integral component of the RSR.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ribosomas / Estrés Fisiológico / Quinasas Quinasa Quinasa PAM / Inflamasomas / Piroptosis / Proteínas NLR Límite: Humans Idioma: En Revista: Science Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ribosomas / Estrés Fisiológico / Quinasas Quinasa Quinasa PAM / Inflamasomas / Piroptosis / Proteínas NLR Límite: Humans Idioma: En Revista: Science Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos