NFκB and IκBα Engage in an ‘I Fold You, You Fold Me’ Interaction Excluding DNA

Binding of IκBα to NFκB robustly causes cessation of NFκB signalling. This phenomenon is facilitated by the sequestering of p50/p65 NFκB dimers in the cytosol via IκBα's masking of the p65 NLS. Interestingly, IκBα is one of the genes upregulated by NFκB binding to its promoter upon translocation into the nucleus; IκBα then facilitates dissociation of NFκB from DNA, creating a negative feedback loop to turn off the NFκB response. NFκB dimers consist of two domains, a dimerization domain and an N-terminal domain (NTD), which are responsible for dimerization/IκBα binding and DNA binding respectively.