Current Drug Targets

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


Insights into Targeting NEMO for Pharmacological Regulation

Author(s): Hong-Xi Chu, Jun-Feng Zhu, Jing-Jie Huang, Zheng-Yu Jiang, Meng-Chen Lu, Xiao-Jin Zhang, Hao-Peng Sun, Qi-Dong You.


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.

Keywords: IKKγ/NEMO, IKK activation model, K63-linked polyubiquitin chains, linear polyubiquitin chains, NEMO-binding domain (NBD), oligomerzation states, protein-protein interactions.

Order Reprints Order Eprints Rights & PermissionsPrintExport

Article Details

Year: 2014
Page: [874 - 887]
Pages: 14
DOI: 10.2174/1389450115666140804215119
Price: $58