Herpes virus proteins BICP0 and BICP0 can activate NF-κB by catalyzing IκBα ubiquitination

The immediate early proteins ICPO and BICPO from Herpes virus are promiscuous activators of both viral and cellular genes and play a critical role in virus life cycle. Here we report that ICPO and BICPO could induce NF-kappaB translocation from cytoplasm into nucleus and strongly activate NF-kappaB responsive genes specifically. This process was dependent on the RING domain of both proteins. In addition, ICPO interacted specifically with IkappaBalpha and its activating effect was attenuated by Ubch5A(C85A) and MG132, but not by IkappaBalpha(S32A/S36A). Remarkably, IkappaBalpha was poly-ubiquitinated by both ICPO and BICPO, in vitro and in vivo. These data indicate that ICPO and BICPO, functioning as ubiquitin ligases, are bona fide activators of NF-kappaB signaling pathway. Our study identifies a new way ICPO and BICPO explore to regulate gene expression. (C) 2004 Elsevier Inc. All rights reserved.