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PMID:19763173

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Citation

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

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.

Links

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

Keywords

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

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CAEEL:Q95XY4

involved_in

GO:0006364: rRNA processing

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:P53254

P

Seeded From UniProt

complete

CAEEL:Q95XY4

located_in

GO:0005730: nucleolus

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q8R5K4

C

Seeded From UniProt

complete

CAEEL:Q95XY4

enables

GO:0003723: RNA binding

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q8R5K4

F

Seeded From UniProt

complete

CAEEL:Q95XY4

located_in

GO:0000794: condensed nuclear chromosome

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q8R5K4

C

Seeded From UniProt

complete

CAEEL:Q95XY4

involved_in

GO:0045824: negative regulation of innate immune response

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00000002

P

Seeded From UniProt

complete

See also

References

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