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A Novel Mechanism to Inhibit NF-κB Signaling Pathway Was Revealed
2016-03-25 | A A A  [print][close]

The NF-κB signaling network, which is an ancient signaling pathway, plays a pivotal role in innate immunity that constitutes a first line of defense against invading pathogens including viruses. However, numerous viruses possess evolved strategies to antagonize the activation of NF-κB signaling pathway.


In recent study, the research group of zoonotic diseases led by Prof. Hanzhong Wang demonstrated that EV71 2C interacts with all isoforms of protein phosphatase 1 (PP1) catalytic subunit (PP1α, PP1β and PP1γ) through PP1 docking motifs. EV71 2C has no influences on subcellular localization of PP1. In addition, the PP1-binding-deficient EV71 2C mutant 3E3L nearly completely lose the ability to suppress IKKβ phosphorylation and markedly restore NF-κB activation, thereby indicating that PP1-binding is efficient for EV71 2C-mediated inhibition of IKKβ phosphorylation and NF-κB activation. They further demonstrated that 2C forms a complex with PP1 and IKKβ to dephosphorylate IKKβ.


Notably, they revealed that other human enteroviruses including poliovirus (PV), Coxsackie A virus 16 (CVA16), and Coxsackie B virus 3 (CVB3), use 2C proteins to recruit PP1, leading to the inhibition of IKKβ phosphorylation. Their findings indicate that enteroviruses exploit a novel mechanism to inhibit IKKβ phosphorylation by recruiting PP1 and IKKβ to form a complex through 2Cproteins, which ultimately results in the inhibition of NF-κB signaling pathway. These findings may be particularly important for understanding the pathogenicity of enteroviruses.




PP1 binding is crucial for EV71 2C-mediated inhibition of IKKb phosphorylation and NF-kB activation

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