Nucleolar proteins suppress Caenorhabditis elegans innate immunity by inhibiting p53/CEP-1.
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.
Fuhrman
Laura E
LE
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America.
Goel
Ajay Kumar
AK
Smith
Jason
J
Shianna
Kevin V
KV
Aballay
Alejandro
A
D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D016923:Cell Death; D004926:Escherichia coli / Q000502:physiology; D055785:Gene Knockdown Techniques; D017238:Genes, Helminth; D007113:Immunity, Innate / Q000276:immunology*; D008136:Longevity; D009687:Nuclear Proteins / Q000378:metabolism*; D034622:RNA Interference; D019779:Salmonella enterica / Q000276:immunology / Q000502:physiology; D013489:Suppression, Genetic; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000235:genetics
C438244:CEP-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53