Figure 1: ALS-associated OPTN mutants fail to suppress NF-κB activity. | Nature Communications

Figure 1: ALS-associated OPTN mutants fail to suppress NF-κB activity.

From: Linear ubiquitination is involved in the pathogenesis of optineurin-associated amyotrophic lateral sclerosis

Figure 1

(a) Domain structure of OPTN and disease-associated mutations. CC, coiled-coil; LZ, leucine zipper; LIR, LC3-interacting region; NZF, Npl4-type zinc finger; UBAN, ubiquitin binding in A20-binding IκB (ABIN) and NEMO proteins. Blue, ALS-associated mutations; pink, POAG-associated mutations. (b) Effects of WT and mutants of OPTN on LUBAC- and TNF-α-induced NF-κB activation were examined by luciferase assays in HEK293T cells. Expression of WT and mutants of FLAG-OPTNs is shown by immunoblotting. (c) Effects of WT and E478G mutant of OPTN on linear diubiquitin-conjugated NEMO were examined as in b. (b,c) Induction folds of NF-κB activity by luciferase assay are shown as mean±s.e.m. (n=3). Statistical significance was assessed using one-way analysis of variance. *P<0.001 and **P<0.01, NS, not significant. (d) WT-OPTN, but not the E478G mutant, binds to linear di-ubiquitinated NEMO. Immunoprecipitation and immunoblotting were performed as indicated.

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