IKKβ phosphorylation regulates RPS3 nuclear translocation and NF-κB function during infection with Escherichia coli strain O157:H7

Wan, FY., et al. 2011. Nat. Immunol. 12, 335-43

Speaker: Shu-Ting Lu (呂淑婷)                            Time: 13:00~14:00, Nov. 30, 2011

Commentator: Dr. Lien-I Hor (何漣漪老師)       Place: Room 601

Abstract:

NF-kB is a protein complex found in almost all cell types, and regulates various gene expressions. Rel proteins are well-known subunits of NF-kB, including RelA (p65), RelB, c-Rel, p50 and p52. Ribosomal protein S3 (RPS3), a non-Rel subunit of NF-kB complexes, affects the target gene specificity of NF-kB (1). The authors previously demonstrated that NF-κB function is blocked by binding of RPS3 with virulence factor NleH1 of Escherichia coli strain O157:H7 (2). Here, they further identify how nuclear localization of RPS3 is regulated. After TNF stimulation, they found that activated IKKb may phosphorylate RPS3 at Ser209, then causing RPS3 nuclear translocation. Previous studies have demonstrated that NleH1 may inhibit RPS3 nuclear translocation, and further influence DNA binding activity of NF-kB. In the present study, they found NleH1 altered the substrate specificity of IKKb, blocking the phosphorylation of RPS3, thereby impairing critical RPS3-dependent NF-kB target genes expression. Taken together, NleH1 helps Escherichia coli strain O157:H7 to avoid NF-kB-related immune attack through inhibition of the IKKb-mediated RPS3 phosphorylation at Ser209, suggesting that pathogen may achieve the ability to increase colonization, diarrhea, and mortality through a selective inhibition of NF-κB function via impeding the function of RPS3.

References:

1.      Gao, X. et al. 2009 Bacterial effector binding to ribosomal protein s3 subverts NF-κB function. PLoS Pathog. 5, e1000708.

2.      Wan, F. et al. 2007 Ribosomal protein S3: a KH domain subunit in NF-κB complexes that mediates selective gene regulation. Cell 131, 927–939.