14-3-3 Epsilon Dynamically Interacts with Key Components of Mitogen-Activated Protein Kinase Signal Module for Selective Modulation of the TNF-α-Induced Time Course-Dependent NF-κB Activity

Inflammation is tightly regulated by nuclear factor-kappa B (NF-κB), and if left unchecked excessive NF-κB activation for cytokine overproduction can lead to various pathogenic consequences including carcinogenesis. A proinflammatory cytokine, tumor necrosis factor-α (TNF-α), can be used to explore possible mechanisms whereby unknown functional pathways modulate the NF-κB activity for regulating TNF-α-induced inflammation. Given the multifunctional nature of 14-3-3 family proteins and the recent finding of their presence in the TNF-α/NF-κB pathway network, we used a dual-tagging quantitative proteomic method to first profile the TNF-α-inducible interacting partners of 14-3-3 e, the least characterized 14-3-3 isomer in the family. For the first time, we found that TNF-α stimulation enhances the interactions between 14-3-3 e and some key components in the mitogen-activated protein kinase (MAPK) signal module which is located at the immediate upstream of NF-κB, including transforming growth factor-beta activ...