Stimulating DDX3 expression by serotonin 5-HT receptor 7 through phosphorylation of p53 via the AC-PKA-ERK signaling

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Subcellular Fractionation for ERK Activation Upon Mitochondrial-derived Peptide Treatment
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Subcellular Fractionation for ERK Activation Upon Mitochondrial-derived Peptide Treatment

Published on: September 25, 2017

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Li-Jung Kang1, Khoa V A Nguyen1, Sanung Eom1

  • 1Department of Biotechnology, Chonnam National University, Gwangju, Republic of Korea.

Journal of Cellular Biochemistry
|June 8, 2019
PubMed

Insights

Serotonin 5-HT7 receptor activation upregulates DDX3 expression, enhancing innate immunity against Hepatitis B virus (HBV). This pathway, involving cAMP/AC/PKA/ERK signaling and p53 phosphorylation, offers a novel therapeutic target for HBV infection.

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology
  • Pharmacology

Background:

  • Hepatitis B virus (HBV) infection poses a significant global health challenge.
  • DDX3 is a host factor crucial for innate immune responses against viral pathogens.
  • Understanding host-pathogen interactions is key to developing antiviral strategies.

Purpose of the Study:

  • To investigate the effect of bioactive compounds on DDX3 expression.
  • To elucidate the role of the serotonin 5-HT7 receptor in regulating DDX3.
  • To explore the signaling pathways mediating 5-HT-induced DDX3 expression and its antiviral effects against HBV.

Main Methods:

  • Screening of 20 bioactive compounds for effects on DDX3.
  • Luciferase assays, RT-PCR, and Western blot analysis to assess DDX3 promoter activity and expression.
  • siRNA-mediated knockdown of 5-HT7 receptor and pharmacological inhibition of signaling pathways (cAMP/AC/PKA/ERK).

Main Results:

  • 5-HT upregulated DDX3 promoter activity via the 5-HT7 receptor in HepG2 cells.
  • 5-HT7 receptor activation by agonist AS-19 increased IFN-β expression and inhibited HBV replication.
  • The 5-HT7 receptor mediates DDX3 expression through cAMP/AC/PKA/ERK pathways, involving p53 phosphorylation.

Conclusions:

  • The 5-HT7 receptor is a novel target for enhancing innate immune responses against HBV.
  • Activation of the 5-HT7 receptor promotes DDX3 expression and antiviral activity via specific signaling cascades.
  • This study identifies a promising therapeutic avenue for managing Hepatitis B virus infection.
Keywords:
AS-19DDX3 promotercAMP pathwayshepatitis Bp53serotonin 5-HT

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