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Polo-like kinase 1 (PLK1) regulates interferon (IFN) induction by MAVS

Damien Vitour1, Stéphanie Dabo1, Malek Ahmadi Pour1

  • 1Unit of Hepacivirus and Innate Immunity, 75015, Paris, France.

The Journal of Biological Chemistry
|June 24, 2009
PubMed

Insights

Polo-like kinase 1 (PLK1) inhibits interferon (IFN) production by binding to the MAVS protein, a key adapter in innate immunity signaling pathways. This discovery reveals PLK1 as a novel regulator of IFN induction.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Mitochondria-bound adapter MAVS is crucial for interferon (IFN) induction via NF-kappaB and IRF3 pathways.
  • MAVS recruits downstream partners like TRAF family members to initiate signaling cascades.

Purpose of the Study:

  • To identify MAVS-interacting proteins and elucidate their role in IFN induction.
  • To investigate the function of Polo-like kinase 1 (PLK1) in regulating MAVS-mediated innate immune responses.

Main Methods:

  • Yeast two-hybrid screening to identify MAVS-binding proteins.
  • Co-immunoprecipitation and Western blotting to analyze protein interactions and phosphorylation.
  • Interferon induction assays in response to various stimuli.
  • RNA interference (RNAi) to deplete PLK1 levels.
  • Cell cycle arrest using nocodazole.

Main Results:

  • The Polo-box domain (PBD) of PLK1 was identified as a MAVS-interacting protein.
  • PLK1 binds to MAVS through both phosphodependent and phosphoindependent mechanisms.
  • PLK1 inhibits MAVS-mediated activation of IRF3 and NF-kappaB pathways, thereby suppressing IFN induction.
  • Depletion of PLK1 enhances IFN induction, particularly under conditions of cell cycle arrest.
  • PLK1's phosphoindependent interaction with MAVS disrupts TRAF3 binding, inhibiting downstream signaling.

Conclusions:

  • PLK1 acts as a novel negative regulator of IFN induction by directly inhibiting MAVS function.
  • The interaction between PLK1 and MAVS offers a potential target for therapeutic interventions to boost innate immunity.

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