Editor-in-Chief: Francis J. Castellino Kleiderer-Pezold Professor of Biochemistry Director, W.M. Keck Center for Transgene Research Dean Emeritus, College of Science 230 Raclin-Carmichael Hall, University of Notre Dame Notre Dame, IN 46556 USA
Affiliation: China Pharmaceutical University, Nanjing 210009, China.
NF-κB essential modulator (NEMO), the non-catalytic regulatory subunit of the IκB kinase (IKK) complex, is essential for the canonical NF-κB activation pathway. It has been identified as a molecular platform for assembling the IKK complex and recruiting upstream IKK activators. However, the exact mechanism for regulating IKK activity has still remained elusive. This review describes structural and functional characteristics of NEMO protein, covers the feasible polyubiquitin-mediated NEMO-dependent IKK complex activation mechanism, and briefly summarizes some proteins that bind to NEMO for enhancing or suppressing IKK complex activity. Furthermore, it also discusses several bioactive compounds that disrupt the protein-protein interactions (PPI) involving NEMO, as these PPI may act as alternative routes to develop novel pharmacological agents for inflammation and cancer therapy.