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USP21 Deubiquitinase Regulates AIM2 Inflammasome Activation.
Hong, Yujin; Lee, Seong-Ok; Oh, Changhoon; Kang, Kwonyoon; Ryoo, Jeongmin; Kim, Dongyoung; Ahn, Kwangseog.
Afiliação
  • Hong Y; School of Biological Sciences, Seoul National University, Seoul, Republic of Korea.
  • Lee SO; Center for RNA Research, Institute for Basic Science, Seoul, Republic of Korea; and.
  • Oh C; School of Biological Sciences, Seoul National University, Seoul, Republic of Korea.
  • Kang K; Center for RNA Research, Institute for Basic Science, Seoul, Republic of Korea; and.
  • Ryoo J; School of Biological Sciences, Seoul National University, Seoul, Republic of Korea.
  • Kim D; Center for RNA Research, Institute for Basic Science, Seoul, Republic of Korea; and.
  • Ahn K; College of Medicine, The Catholic University, Seoul, Republic of Korea.
J Immunol ; 207(7): 1926-1936, 2021 10 01.
Article em En | MEDLINE | ID: mdl-34470856
ABSTRACT
Innate immune sensing of cytosolic DNA via absent in melanoma 2 (AIM2) is a key mechanism leading to inflammatory responses. As aberrant immune responses by dysregulated AIM2 are associated with autoinflammatory diseases, activation of the AIM2 inflammasome should be tightly controlled. In this study, we discovered that ubiquitination and deubiquitination of AIM2 are critical events that regulate AIM2 inflammasome activation. In resting human macrophage cells, AIM2 is constitutively ubiquitinated and undergoes proteasomal degradation to avoid autoinflammation. Upon DNA stimulation, USP21 binds to AIM2 and deubiquitinates it, thereby increasing its protein stability. In addition to the role of USP21 in regulating AIM2 turnover, we uncovered that USP21-mediated deubiquitination of AIM2 is required for the assembly of the AIM2 inflammasome. Depletion of USP21 does not affect the DNA-binding ability of AIM2 but inhibits the formation of the AIM2-ASC complex. Our findings establish that fine-tuning of AIM2 by the ubiquitin system is important for regulating AIM2 inflammasome activation.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ubiquitina Tiolesterase / Proteínas de Ligação a DNA / Inflamassomos / Inflamação / Macrófagos Limite: Humans Idioma: En Revista: J Immunol Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ubiquitina Tiolesterase / Proteínas de Ligação a DNA / Inflamassomos / Inflamação / Macrófagos Limite: Humans Idioma: En Revista: J Immunol Ano de publicação: 2021 Tipo de documento: Article