Fig. 8

Schematic representation of OTULIN regulating the NF-κB pathway in ischemic stroke. Ischemic stroke induced rapid activation of the NF-κB pathway, mainly shown by the activation of IKKs, the degradation and phosphorylation of IκBα, and the increased nuclear translocation of NF-κB p65. The activated NF-κB pathway leads to microglial activation along with a sharp increase in the production of pro-inflammatory cytokines and the occurrence of inflammatory responses in the brain. LUBAC, which consists of HOIP, HOIL-1, and SHARPIN, participates in the assembly of ubiquitin chains on IKK complexes. The deubiquitinase OTULIN interacts with HOIP to cleave the Met-1 Ub on IKKγ, thus resulting in depression of the NF-κB pathway. OTULIN overexpression obviously inhibited the excessive activation of microglia and the production of inflammatory responses through suppressing the phosphorylation and degradation of IκBα and subsequently attenuating the nuclear translocation of NF-κB p65