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Nucleolar proteins suppress Caenorhabditis elegans innate immunity by inhibiting p53/CEP-1

Laura E Fuhrman1, Ajay Kumar Goel, Jason Smith

  • 1Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America.

Plos Genetics
|September 19, 2009
PubMed

Insights

The nucleolus regulates innate immunity against bacterial infections. Inhibiting nucleolar proteins like NOL-6 activates the p53/CEP-1 pathway, enhancing immune response.

Area of Science:

  • * Molecular Biology
  • * Immunology
  • * Genetics

Background:

  • * The tumor suppressor p53 is crucial for various cellular functions, including aging and cell cycle regulation.
  • * Innate immunity relies on complex regulatory networks to combat pathogens.
  • * Nucleolar proteins, such as NOL-6, are involved in ribosome biogenesis and are conserved across species.

Purpose of the Study:

  • * To investigate the role of nucleolar proteins in regulating innate immunity.
  • * To identify genetic factors that modulate immune responses in Caenorhabditis elegans.
  • * To elucidate the molecular mechanisms linking nucleolar function to immune activation.

Main Methods:

  • * Genetic screening in Caenorhabditis elegans to identify immune regulators.
  • * Mutation and silencing of NOL-6 and other nucleolar proteins.
  • * Genome-wide microarray analysis to assess gene expression changes.
  • * Investigating the involvement of p53 homologue CEP-1 and its target SYM-1.

Main Results:

  • * Mutations in NOL-6, a nucleolar RNA-associated protein (NRAP), confer enhanced resistance to bacterial infections.
  • * Silencing of NOL-6 and other nucleolar proteins leads to increased transcriptional levels of p53/CEP-1-regulated genes.
  • * Activation of innate immunity by nucleolar protein inhibition requires the p53/CEP-1 pathway and its target SYM-1.

Conclusions:

  • * The nucleolus plays a conserved role in regulating innate immune responses against bacterial pathogens.
  • * Inhibition of nucleolar function activates the p53/CEP-1 pathway, enhancing immunity.
  • * This study reveals an ancient immune mechanism involving the nucleolus and p53/CEP-1.

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