Epstein-Barr virus-transforming protein latent infection membrane protein 1 activates transcription factor NF-κB through a pathway that includes the NF-κB-inducing kinase and the IκB kinases IKKα and IKKβ

The Epstein-Barr virus oncoprotein latent infection membrane protein 1 (LMP1) is a constitutively aggregated pseudo-tumor necrosis factor receptor (TNFR) that activates transcription factor NF-kappa B through two sites in its C-terminal cytoplasmic domain. One site is similar to activated TNFRII in associating,vith TNFR-associated factors TRAF1 and TRAF2, and the second site is similar to TNFRI in associating with the TNFRI death domain interacting protein TRADD. TNFRI has been recently shown to activate NF-kappa B through association with TRADD, RIP, and TRAF2; activation of the NF-kappa B-inducing kinase (NIK); activation of the I kappa B alpha kinases (IKK alpha and IKK beta); and phosphorylation of I kappa B alpha. I kappa B alpha phosphorylation on Ser-32 and Ser-36 is followed by its degradation and NF-kappa B activation. In this report, we show that NF-kappa B activation by LMP1 or by each of its effector sites is mediated by a pathway that includes NIK IKK alpha, and IKK beta. Dominant negative mutants of NIK, IKK alpha, or IKK beta substantially inhibited NF-kappa B activation by LMP1 or by each of its effector sites.