NFAT1 is known for its roles in T cell development and activation. So far, the phosphorylation of NFAT1 has been extensively studied, but the other post-translational modifications of NFAT1 remain largely unknown. In this study, we reported that NFAT1 is a linearly ubiquitinated substrate of linear ubiquitin chain assembly complex (LUBAC). LUBAC promoted NFAT1 linear ubiquitination, which in turn inhibited K48-linked polyubiquitination of NFAT1 and therefore increased NFAT1 protein stability. Interestingly, the linear ubiquitination levels of NFAT1 in patients with the Kawasaki disease were upregulated. Further studies demonstrated that the patients with the Kawasaki disease had increased mRNA levels of HOIL-1L. These findings revealed a linearly ubiquitinated substrate of LUBAC and an important biological function of NFAT1 linear ubiquitination in the Kawasaki disease and therefore may provide a novel strategy for the treatment of the Kawasaki disease.
Keywords: Kawasaki disease; LUBAC; NFAT1; linear ubiquitination; protein stability.
© 2023 Federation of European Biochemical Societies.