Cover Picture: NF-kB activation is an important cellular response to genotoxic stress. The signaling cascade transducing nuclear DNA damage signals through retrograde nuclear-to-cytoplasmic signaling to activate NF-kB. This signaling cascade involves a variety of posttranslational modifications, such as SUMOylation, ubiquitylation and phosphorylation, of several key proteins including ATM. NEMO, TRAF6, and ELKS. The sequential modifications of NEMO guide its cytoplasmic/nuclear localization which bridges the nuclear DNA damage and cytoplasmic NF-kB activation. Activated NF-kB then translocates into the nucleus, and drive transactivation of anti-apoptotic genes, inflammatory cytokines, and oncogenic miRNAs, resulting in therapeutic resistance and aggressive metastasis in cancer cells.
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