OTULIN deficiency in ORAS causes cell type‐specific LUBAC degradation, dysregulated TNF signalling and cell death

A

Immunoblot analysis of IκBα phosphorylation and degradation as well as p65/RelA phosphorylation in healthy control or OTULIN^G281R fibroblasts primary fibroblasts in response to stimulation with TNF (10 ng/ml). Data are representative of three independent experiments.

B

Immunoblot analysis of phosphorylation of the MAP kinases p38 and JNK in healthy control or OTULIN^G281R primary fibroblasts in response to stimulation with TNF (10 ng/ml). Data are representative of three independent experiments.

C

Densitometry analysis of p65/RelA phosphorylation as presented in (A) from three independent experiments.

D

ELISA analysis of IL‐8 secretion in response to TNF stimulation (10 ng/ml) in healthy control or OTULIN^G281R primary fibroblasts. Bars represent mean ± SEM (n = 4).

E

Immunoblot analysis of the native TNF‐RSC purified by immunoprecipitation from healthy control or OTULIN^G281R primary fibroblasts. Data are representative of three independent experiments.

Figure 4. TNF‐induced NF‐κB and MAP kinase activation is impaired in OTULING 281R fibroblasts due to reduced LUBAC recruitment to the TNF‐RSC .

Figure 4. TNF‐induced NF‐κB and MAP kinase activation is impaired in OTULIN^G ^281R fibroblasts due to reduced LUBAC recruitment to the TNF‐RSC .