SUMOylation-Dependent Localization of IKKε in PML Nuclear Bodies Is Essential for Protection against DNA-Damage-Triggered Cell Death

The IKK-related kinase IKK epsilon contributes to the antiviral response and can function as an oncogene that is frequently amplified in breast cancer. Here we report on an additional role of IKK epsilon as a mediator protecting from DNA-damage-induced cell death. Genotoxic stress allows for kinase-dependent entry of IKK epsilon into the nucleus, where IKK epsilon-dependent PML phosphorylation is a prerequisite for retention of this kinase in PML nuclear bodies. Within these subnuclear structures IKK epsilon inducibly colocalizes with TOPORS, which functions as a SUMO E3 ligase mediating SUMOylation of IKK epsilon at lysine 231. SUMO modification of IKK epsilon is required to trigger phosphorylation of nuclear substrates including NF-kappa B p65, thereby contributing to the antiapoptotic function of NF-kappa B in response to DNA damage.