Metalloprotease NleC Suppresses Host NF-κB/Inflammatory Responses by Cleaving p65 and Interfering with the p65/RPS3 Interaction

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The nuclear factor kappaB (NF-κB) signaling pathway is crucial for host defense, as it orchestrates both innate and adaptive immune responses. Beyond the best-studied Rel proteins (p65, RelB, c-Rel, p50 and p52), RPS3 has been recently identified as a “specifier” component of NF-κB, modulating the promoter selectivity and transcriptional specificity of NF-κB. In particular, the RPS3/p65-conferred signaling pathway was recently shown to play a critical role in host proinflammatory transcription and immune responses. Attaching and effacing (A/E) pathogens and others have acquired sophisticated mechanisms to modulate host NF-κB signaling pathways. We have found that NleC, a metalloprotease effector secreted by A/E pathogens, modulates host NF-κB signaling and inflammatory responses through a novel mechanism. NleC specifically recognizes and cleaves a small percentage of p65 and the generated N-terminal fragment of p65 interferes with the p65/RPS3 interaction, thereby amplifying the effect of cleaving only a small percentage of p65 molecules to selectively inhibit NF-κB gene expression. Our findings highlight a previously unappreciated mechanism through which pathogen-encoded proteases interfere with signaling cascades and inflammatory responses in host cells.

Vyšlo v časopise: Metalloprotease NleC Suppresses Host NF-κB/Inflammatory Responses by Cleaving p65 and Interfering with the p65/RPS3 Interaction. PLoS Pathog 11(3): e32767. doi:10.1371/journal.ppat.1004705
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004705

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