Non-catalytic ubiquitin binding by A20 prevents psoriatic arthritis-like disease and inflammation View Full Text


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Article Info

DATE

2020-03-16

AUTHORS

Bahram Razani, Michael I Whang, Francis S Kim, Mary C Nakamura, Xiaofei Sun, Rommel Advincula, Jessie A Turnbaugh, Mihir Pendse, Priscilia Tanbun, Philip Achacoso, Peter J Turnbaugh, Barbara A Malynn, Averil Ma

ABSTRACT

A20 is an anti-inflammatory protein that is strongly linked to human disease. Here, we find that mice expressing three distinct targeted mutations of A20's zinc finger 7 (ZF7) ubiquitin-binding motif uniformly developed digit arthritis with features common to psoriatic arthritis, while mice expressing point mutations in A20's OTU or ZF4 motifs did not exhibit this phenotype. Arthritis in A20ZF7 mice required T cells and MyD88, was exquisitely sensitive to tumor necrosis factor and interleukin-17A, and persisted in germ-free conditions. A20ZF7 cells exhibited prolonged IκB kinase activity that drove exaggerated transcription of late-phase nuclear factor-κB response genes in vitro and in prediseased mouse paws in vivo. In addition, mice expressing double-mutant A20 proteins in A20's ZF4 and ZF7 motifs died perinatally with multi-organ inflammation. Therefore, A20's ZF4 and ZF7 motifs synergistically prevent inflammatory disease in a non-catalytic manner. More... »

PAGES

422-433

References to SciGraph publications

  • 2004-08-29. The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses in NATURE IMMUNOLOGY
  • 2018-08-14. The Immunologic Role of IL-17 in Psoriasis and Psoriatic Arthritis Pathogenesis in CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY
  • 2015-05-04. The ubiquitin-modifying enzyme A20 restricts the ubiquitination of RIPK3 and protects cells from necroptosis in NATURE IMMUNOLOGY
  • 2015-12-07. Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early onset autoinflammatory syndrome in NATURE GENETICS
  • 2004-07-18. De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-κB signalling in NATURE
  • 2019-05-06. Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry in NATURE IMMUNOLOGY
  • 2019-05-13. A20 prevents inflammasome-dependent arthritis by inhibiting macrophage necroptosis through its ZnF7 ubiquitin-binding domain in NATURE CELL BIOLOGY
  • 2015-12-09. Phosphorylation and linear ubiquitin direct A20 inhibition of inflammation in NATURE
  • 2007-06. Cytokines in the pathogenesis of rheumatoid arthritis in NATURE REVIEWS IMMUNOLOGY
  • 2011-10-23. Dendritic cell expression of A20 preserves immune homeostasis and prevents colitis and spondyloarthritis in NATURE IMMUNOLOGY
  • 2009-02-08. The stability of mRNA influences the temporal order of the induction of genes encoding inflammatory molecules in NATURE IMMUNOLOGY
  • 2011-08-14. A20 (TNFAIP3) deficiency in myeloid cells triggers erosive polyarthritis resembling rheumatoid arthritis in NATURE GENETICS
  • 2007-11-04. Two independent alleles at 6q23 associated with risk of rheumatoid arthritis in NATURE GENETICS
  • 2014-06-29. Negative regulation of the NLRP3 inflammasome by A20 protects against arthritis in NATURE
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41590-020-0634-4

    DOI

    http://dx.doi.org/10.1038/s41590-020-0634-4

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1125674092

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/32205880


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