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Fuhrman, LE, Goel, AK, Smith, J, Shianna, KV and Aballay, A (2009) Nucleolar proteins suppress Caenorhabditis elegans innate immunity by inhibiting p53/CEP-1. PLoS Genet. 5:e1000657


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.


PubMed PMC2734340 Online version:10.1371/journal.pgen.1000657


Animals; Caenorhabditis elegans/cytology; Caenorhabditis elegans/genetics; Caenorhabditis elegans/immunology; Caenorhabditis elegans/microbiology; Caenorhabditis elegans Proteins/antagonists & inhibitors; Caenorhabditis elegans Proteins/genetics; Caenorhabditis elegans Proteins/metabolism; Cell Death; Escherichia coli/physiology; Gene Knockdown Techniques; Genes, Helminth; Immunity, Innate/immunology; Longevity; Nuclear Proteins/metabolism; RNA Interference; Salmonella enterica/immunology; Salmonella enterica/physiology; Suppression, Genetic; Transcription, Genetic; Tumor Suppressor Protein p53/antagonists & inhibitors; Tumor Suppressor Protein p53/genetics