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Working model for the role of Lys-195 in TNFα-induced RelA polyubiquitination and degradation. TNFα induces IKKβ-mediated IκBα degradation and NF-κB nuclear translocation. Once bound to the NF-κB-binding site on the promoter, the RelA subunit of NF-κB is polyubiquitinated at Lys-195 and subsequently degraded to attenuate TNFα-induced NF-κB activation. R1, TNFα receptor 1; DD, death domain.
