The fructose-2,6-bisphosphatase TIGAR suppresses NF-κB signaling by directly inhibiting the linear ubiquitin assembly complex LUBAC.

ABSTRACT: The systems integration of whole-body metabolism and immune signaling are central homeostatic mechanisms necessary for maintenance of normal physiology, and dysregulation of these processes leads to a variety of chronic disorders. However, the intracellular mechanisms responsible for cell-autonomous cross-talk between the inflammatory signaling pathways and metabolic flux have remained enigmatic. In this study, we discovered that the fructose-2,6-bisphosphatase TIGAR (Tp53-induced glycolysis and apoptosis regulator) critically regulates NF-κB activation. We found that TIGAR potently inhibits NF-κB-dependent gene expression by suppressing the upstream activation of IKKβ phosphorylation and kinase activation. This inhibition occurred through a direct binding competition between NEMO and TIGA

SUBMITTER: Tang Y 

PROVIDER: S-EPMC5961042 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature