β-Arrestin2 functions as a phosphorylation-regulated suppressor of UV-induced NF-κB activation

NF-kappa B activation is an important mechanism of mammalian UV response to protect cells. UV-induced NF-kappa B activation depends on the casein kinase II (CK2) phosphorylation of I kappa B alpha at a cluster of C-terminal sites, but how it is regulated remains unclear. Here we demonstrate that beta-arrestin2 can function as an effective suppressor of UV-induced NF-kappa B activation through its direct interaction with I kappa B alpha. CK2 phosphorylation of beta-arrestin2 blocks its interaction with I kappa B alpha and abolishes its suppression of NF-kappa B activation, indicating that the beta-arrestin2 phosphorylation is critical. Moreover, stimulation of beta(2)-adrenergic receptors, a representative of G-protein-coupled receptors in epidermal cells, promotes dephosphorylation of beta-arrestin2 and its suppression of NF-kappa B activation. Consequently, the beta-arrestin2 suppression leads to promotion of UV-induced cell death, which is also under regulation of beta-arrestin2 phosphorylation. Thus, beta-arrestin2 is identified as a phosphorylation-regulated suppressor of UV response and this may play a functional role in the response of epidermal cells to UV.