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Phosphorylation drives an apoptotic protein to activate antiapoptotic genes: paradigm of influenza A matrix 1 protein

Umesh Chandra Halder1, Rahul Bhowmick1, Tapasi Roy Mukherjee1

  • 1Division of Virology, National Institute of Cholera and Enteric Diseases, P-33 C.I.T. Road, Scheme-XM, Beliaghata, Kolkata 700010, India.

The Journal of Biological Chemistry
|April 4, 2013
PubMed

Insights

Influenza A virus M1 protein surprisingly promotes cell survival by blocking Daxx-mediated gene repression. This finding reveals a new role for M1 in viral infection and suggests potential therapeutic targets.

Area of Science:

  • Virology
  • Molecular Biology
  • Immunology

Background:

  • Viral proteins modulate host cell pathways controlling immunity and cell death.
  • Influenza A virus matrix 1 protein (M1) is known to induce apoptosis but may have other functions.

Purpose of the Study:

  • To investigate the role of influenza A virus M1 protein in regulating host cell survival pathways during infection.
  • To elucidate the mechanism by which M1 protein influences gene expression related to innate immunity and cell death.

Main Methods:

  • Assessed the interaction between M1 protein and Death domain-associated protein 6 (Daxx).
  • Analyzed the effect of M1-Daxx interaction on RelB-mediated gene transcription and DNA methylation.
  • Investigated the role of M1 nuclear translocation and its dependence on cellular kinases.

Main Results:

  • M1 protein binds to and stabilizes Daxx, preventing its degradation and subsequent repression of survival genes (cIAP1, cIAP2, cFLIP).
  • M1 binding to Daxx inhibits the recruitment of RelB and DNA methyltransferases (Dnmt1, Dnmt3a) to gene promoters, leading to gene activation.
  • Nuclear translocation of M1, dependent on kinase phosphorylation, is crucial for this survival-promoting function, as shown by the effect of protein kinase C inhibition.

Conclusions:

  • Influenza A virus M1 protein exhibits a novel survival role by antagonizing Daxx-mediated gene repression.
  • The interaction between M1 and Daxx modulates host cell innate immune responses and cell death pathways.
  • Understanding this dual function of M1 provides potential therapeutic targets for limiting influenza virus infection.
Keywords:
DNA MethylationDNA MethyltransferaseDeath Domain-associated Protein 6 (Daxx)Influenza VirusInhibitor of Apoptosis (IAP)Matrix 1 ProteinNF-κB Transcription FactorNuclear TranslocationPhosphorylationRelB

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