Background: NF-κB regulates transcription via binding to DNA and interactions with cofactors. Results: NF-κB binding to DNA and cytosolic IκBs is conserved, whereas binding to nuclear IκBs has evolved. Conclusion: There is distinct evolutionary pressure on two NF-κB/IκB binding interfaces. Significance: The results provide inroads into IκB-specific modulation of NF-κB activity.
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