Lymphotoxin-β receptor mediates NEMO-independent NF-κB activation

Lymphotoxin-beta receptor (LTbetaR) is a member of the tumor necrosis factor receptor (TNFR) superfamily that activates nuclear factor-kappaB (NF-kappaB) through the IkappaB kinase (IKK) complex, the core of which is comprised of IKK1, IKK2 and NF-kappaB essential modulator (NEMO). We demonstrate here that the LTbetaR signaling to NF-kappaB activation does not necessarily require NEMO, which is essential for TNFR signaling. In the absence of NEMO, the p50 and RelB, but not ReIA subunits of NF-kappaB are found in the nuclear DNA binding complexes induced by the LTOR signaling. Our results thus disclose NEMO-independent NF-kappaB activation by LTbetaR. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.