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PKC alpha regulates Sendai virus-mediated interferon induction through HDAC6 and β-catenin.

Publication ,  Journal Article
Zhu, J; Coyne, CB; Sarkar, SN
Published in: EMBO J
September 27, 2011

Recognition of viral RNA by cytoplasmic retinoic acid inducible gene I (RIG-I)-like receptors initiates signals leading to the induction of type I interferon (IFN) transcription via transcription factors such as interferon regulatory factor 3 (IRF3) and nuclear factor κB (NF-κB). Here, we describe a new signalling pathway that involves protein kinase C alpha (PKCα), histone deacetylase 6 (HDAC6) and beta-catenin (β-catenin), which is essential for IFN gene induction following virus infection. Knockdown of PKCα in various human cells, including primary cells, inhibited Sendai virus (SeV)-mediated IFN induction and enhanced virus replication. In the absence of this pathway IRF3 becomes activated, but does not bind to its promoter and is thus unable to support transcription. Mechanistically, SeV infection induced the activation of PKCα, which promoted its interaction with HDAC6 and enhanced its deacetylation activity in a phosphorylation-dependent manner. Further downstream, HDAC6 caused deacetylation of β-catenin and enhanced its nuclear translocation and promoter binding. In the nucleus, β-catenin acted as a co-activator for IRF3-mediated transcription. Our findings suggest an important role of a novel signalling pathway mediated by PKCα-HDAC6-β-catenin in controlling IRF3-mediated transcription.

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Published In

EMBO J

DOI

EISSN

1460-2075

Publication Date

September 27, 2011

Volume

30

Issue

23

Start / End Page

4838 / 4849

Location

England

Related Subject Headings

  • beta Catenin
  • Virus Replication
  • Signal Transduction
  • Sendai virus
  • RNA, Small Interfering
  • Protein Kinase C-alpha
  • Phosphorylation
  • NF-kappa B
  • Interferon Type I
  • Interferon Regulatory Factor-3
 

Citation

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Zhu, J., Coyne, C. B., & Sarkar, S. N. (2011). PKC alpha regulates Sendai virus-mediated interferon induction through HDAC6 and β-catenin. EMBO J, 30(23), 4838–4849. https://doi.org/10.1038/emboj.2011.351
Zhu, Jianzhong, Carolyn B. Coyne, and Saumendra N. Sarkar. “PKC alpha regulates Sendai virus-mediated interferon induction through HDAC6 and β-catenin.EMBO J 30, no. 23 (September 27, 2011): 4838–49. https://doi.org/10.1038/emboj.2011.351.
Zhu J, Coyne CB, Sarkar SN. PKC alpha regulates Sendai virus-mediated interferon induction through HDAC6 and β-catenin. EMBO J. 2011 Sep 27;30(23):4838–49.
Zhu, Jianzhong, et al. “PKC alpha regulates Sendai virus-mediated interferon induction through HDAC6 and β-catenin.EMBO J, vol. 30, no. 23, Sept. 2011, pp. 4838–49. Pubmed, doi:10.1038/emboj.2011.351.
Zhu J, Coyne CB, Sarkar SN. PKC alpha regulates Sendai virus-mediated interferon induction through HDAC6 and β-catenin. EMBO J. 2011 Sep 27;30(23):4838–4849.

Published In

EMBO J

DOI

EISSN

1460-2075

Publication Date

September 27, 2011

Volume

30

Issue

23

Start / End Page

4838 / 4849

Location

England

Related Subject Headings

  • beta Catenin
  • Virus Replication
  • Signal Transduction
  • Sendai virus
  • RNA, Small Interfering
  • Protein Kinase C-alpha
  • Phosphorylation
  • NF-kappa B
  • Interferon Type I
  • Interferon Regulatory Factor-3