Herpes virus proteins ICP0 and BICP0 can activate NF-κB by catalyzing IκBα ubiquitination

The immediate early proteins ICP0 and BICP0 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 ICP0 and BICP0 could induce NF-κB translocation from cytoplasm into nucleus and strongly activate NF-κB responsive genes specifically. This process was dependent on the RING domain of both proteins. In addition, ICP0 interacted specifically with IκBα and its activating effect was attenuated by Ubch5A(C85A) and MG132, but not by IκBα(S32A/S36A). Remarkably, IκBα was poly-ubiquitinated by both ICP0 and BICP0, in vitro and in vivo. These data indicate that ICP0 and BICP0, functioning as ubiquitin ligases, are bona fide activators of NF-κB signaling pathway. Our study identifies a new way ICP0 and BICP0 explore to regulate gene expression.