Oncotarget

Research Papers:

(DEAD)-box RNA helicase 3 modulates NF-κB signal pathway by controlling the phosphorylation of PP2A-C subunit

Xin Wang, Rui Wang, Miao Luo, Chen Li, Hua-Xia Wang, Chang-Chao Huan, Yu-Rong Qu, Ying Liao and Xiang Mao _

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Oncotarget. 2017; 8:33197-33213. https://doi.org/10.18632/oncotarget.16593

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Abstract

Xin Wang1, Rui Wang1, Miao Luo1, Chen Li1, Hua-Xia Wang1, Chang-Chao Huan1, Yu-Rong Qu2, Ying Liao2, Xiang Mao1,2

1College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China

2Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, China

Correspondence to:

Xiang Mao, email: xmao@njau.edu.cn

Ying Liao, email: liaoying@shvri.ac.cn

Keywords: (DEAD)-box RNA helicase 3, PP2A, NF-κB

Received: January 12, 2017     Accepted: March 17, 2017     Published: March 27, 2017

ABSTRACT

Asp-Glu-Ala-Asp (DEAD)-box RNA helicase 3 (DDX3), an ATP-dependent RNA helicase, is associated with RNA splicing, mRNA export, transcription, translation, and RNA decay. Recent studies revealed that DDX3 participates in innate immune response during virus infection by interacting with TBK1 and regulating the production of IFN-β. In our studies, we demonstrated that DDX3 regulated NF-κB signal pathway. We found that DDX3 knockdown reduced the phosphorylation of p65 and IKK-β and ultimately attenuated the production of inflammatory cytokines induced by poly(I:C) or TNF-α stimulation. The regulatory effect of DDX3 on NF-κB signal pathway was not affected by the loss of its ATPase or helicase activity. We further identified PP2A C subunit (PP2A-C) as an interaction partner of DDX3 by co-immunoprecipitation and mass spectrum analysis. We confirmed that DDX3 formed the complex with PP2A-C/IKK-β and regulated the interaction between IKK-β and PP2A-C. Furthermore, we demonstrated that DDX3 modulated the activity of PP2A by controlling the phosphorylation of PP2A-C, which might enable PP2A-C to regulate NF-κB signal pathway by dephosphorylating IKK-β. All these findings suggested DDX3 plays multiple roles in modulating innate immune system.


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