Skip to main content
eScholarship
Open Access Publications from the University of California

UCSF

UC San Francisco Previously Published Works bannerUCSF

Non-catalytic ubiquitin binding by A20 prevents psoriatic arthritis-like disease and inflammation.

  • Author(s): Razani, Bahram
  • Whang, Michael I
  • Kim, Francis S
  • Nakamura, Mary C
  • Sun, Xiaofei
  • Advincula, Rommel
  • Turnbaugh, Jessie A
  • Pendse, Mihir
  • Tanbun, Priscilia
  • Achacoso, Philip
  • Turnbaugh, Peter J
  • Malynn, Barbara A
  • Ma, Averil
  • et al.
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.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
Current View