XEDAR Activates the Non-Canonical NF-κB Pathway

The 2015 study by Verhelst et al. found that the X-linked ectodermal dysplasia receptor (XEDAR) activates the non-canonical NF-κB signaling pathway, which involves the conversion of p100 to p52 and the subsequent movement of p52 and RelB into the nucleus. The activation of this pathway by XEDAR requires the interaction with TRAF3 and TRAF6, as well as the kinase activities of NIK and IKKα. Mutations in XEDAR's TRAF binding sites significantly reduced its ability to activate this signaling pathway. The study also identified that NIK accumulation is induced by XEDAR and that p100 processing is negatively regulated by TRAF3, CIAP1, and A20. These findings enhance the understanding of XEDAR's role in the molecular mechanisms governing non-canonical NF-κB signaling.