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

Laura E. Fuhrman, Ajay Kumar Goel, Jason Smith, Kevin V. Shianna, Alejandro Aballay

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

The tumor suppressor p53 has been implicated in multiple functions that play key roles in health and disease, including ribosome biogenesis, control of aging, and cell cycle regulation. A genetic screen for negative regulators of innate immunity in Caenorhabditis elegans led to the identification of a mutation in NOL-6, a nucleolar RNA-associated protein (NRAP), which is involved in ribosome biogenesis and conserved across eukaryotic organisms. Mutation or silencing of NOL-6 and other nucleolar proteins results in an enhanced resistance to bacterial infections. A full-genome microarray analysis on animals with altered immune function due to mutation in nol-6 shows increased transcriptional levels of genes regulated by a p53 homologue, CEP-1. Further studies indicate that the activation of innate immunity by inhibition of nucleolar proteins requires p53/CEP-1 and its transcriptional target SYM-1. Since nucleoli and p53/CEP-1 are conserved, our results reveal an ancient immune mechanism by which the nucleolus may regulate immune responses against bacterial pathogens.

Original languageEnglish (US)
Article numbere1000657
JournalPLoS Genetics
Volume5
Issue number9
DOIs
StatePublished - Sep 1 2009
Externally publishedYes

Fingerprint

Caenorhabditis elegans
Nuclear Proteins
immunity
Innate Immunity
mutation
cell nucleolus
ribosomes
Ribosomes
Mutation
protein
health and disease
proteins
Microarray Analysis
Cell Cycle Checkpoints
bacterial infections
immune response
Bacterial Infections
tumor
RNA
cell cycle

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

Nucleolar proteins suppress Caenorhabditis elegans innate immunity by inhibiting p53/CEP-1. / Fuhrman, Laura E.; Goel, Ajay Kumar; Smith, Jason; Shianna, Kevin V.; Aballay, Alejandro.

In: PLoS Genetics, Vol. 5, No. 9, e1000657, 01.09.2009.

Research output: Contribution to journalArticle

Fuhrman, Laura E. ; Goel, Ajay Kumar ; Smith, Jason ; Shianna, Kevin V. ; Aballay, Alejandro. / Nucleolar proteins suppress Caenorhabditis elegans innate immunity by inhibiting p53/CEP-1. In: PLoS Genetics. 2009 ; Vol. 5, No. 9.
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