Journal: The EMBO Journal

Article Title: A TNF ‐p100 pathway subverts noncanonical NF ‐κB signaling in inflamed secondary lymphoid organs

doi: 10.15252/embj.201796919

Figure Lengend Snippet: In resting cells, TRAF2:TRAF3:cIAP complex promotes the degradation of NIK, and p100‐IκBδ retains RelB and other NF‐κB monomers. Activation of LTβR leads to the proteolysis of TRAF2 and TRAF3 that rescues NIK from the constitutive degradation. NIK in association with IKK1 induces the processing of p100 into p52 that liberates the RelB heterodimers. TNF signal renders TRAF2 and TRAF3 resistant to degradation in LTβR‐stimulated cells resulting in the inactivation of NIK. In addition, TNF‐activated RelA dimers induce the transcription of Nfkb2 mRNA, which encodes p100. Therefore, TNF treatment of LTβR‐stimulated cells potently accumulates the precursor p100, which sequesters the pre‐existing nuclear RelB dimers as inhibitory IκBδ and terminates RelB‐mediated expressions of homeostatic chemokines. The proposed mechanism impedes continuing ingress of naïve lymphocytes in reactive SLOs.

Article Snippet: RelB DNA binding activity was also measured using TransAM flexi NF‐κB family kit (Cat. No. 43298, Active Motif, USA) according to the manufacturer's instructions.

Techniques: Activation Assay