Insights into Targeting NEMO for Pharmacological Regulation

Title:Insights into Targeting NEMO for Pharmacological Regulation

Volume: 15 Issue: 9

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

Affiliation:

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

Abstract: 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.

Cite this article as:

Chu Hong-Xi, Zhu Jun-Feng, Huang Jing-Jie, Jiang Zheng-Yu, Lu Meng-Chen, Zhang Xiao-Jin, Sun Hao-Peng and You Qi-Dong, Insights into Targeting NEMO for Pharmacological Regulation, Current Drug Targets 2014; 15 (9) . https://dx.doi.org/10.2174/1389450115666140804215119