Fig. 5: Uba1 mutation impairs polyubiquitylation of inflammatory signalling complexes.
From: Independent mechanisms of inflammation and myeloid bias in VEXAS syndrome
a, Immunoblots of Flag immunoprecipitates and input lysates from Uba1+/y or Uba1M41T/y BMDMs treated with Flag–TNF as indicated. b, Immunoblots of denaturing Lys63-polyubiquitin immunoprecipitates and input lysates from Uba1+/y or Uba1M41T/y BMDMs treated for the indicated number of minutes (m). c, Immunoblots of untreated or linear-specific (OTULIN) deubiquitylase-treated Flag immunoprecipitates and input lysates from Uba1+/y or Uba1M41T/y BMDMs treated with Flag–TNF for 5 min. d, Immunoblots of pull-downs using linear polyubiquitin-specific TUBEs and input lysates from LPS-treated BMDMs of the indicated genotypes. e, Proposed model of a feedforward cycle of aberrant HSPC myeloid differentiation and autoinflammation driven by a RIPK1–RIPK3–CASP8 death axis in UBA1-mutant myeloid cells. The diagram was created using BioRender. Experiments in a–d were performed 9 days after electroporation and are representative of three (a) or two (b–d) independent experiments.
