Nuclear IKKβ Is an Adaptor Protein for IκBα Ubiquitination and Degradation in UV-Induced NF-κB Activation

Proinflammatory cytokines activate NF-kappa B using the I kappa B kinase (IKK) complex that phosphorylates inhibitory proteins (I kappa Bs) at N-terminal sites resulting in their ubiquitination and degradation in the cytoplasm. Although ultraviolet (UV) irradiation does not lead to IKK activity, it activates NF-kappa B by an unknown mechanism through I kappa B alpha degradation without N-terminal phosphorylation. Here, we describe an adaptor function of nuclear IKK beta in UV-induced I kappa B alpha degradation. UV irradiation induces the nuclear translocation of I kappa B alpha and association with IKK beta, which constitutively interacts with beta-TrCP through heterogeneous ribonucleoprotein-U (hnRNP-U) leading to I kappa B alpha ubiquitination and degradation. Furthermore, casein kinase 2 (CK2) and p38 associate with IKK beta and promote I kappa B alpha degradation by phosphorylation at C-terminal sites. Thus, nuclear IKK beta acts as an adaptor protein for I kappa B alpha degradation in UV-induced NF-kappa B activation. NF-kappa B activated by the nuclear IKK beta adaptor protein suppresses anti-apoptotic gene expression and promotes UV-induced cell death.