Interference with nuclear factor kappaB signaling pathway by pathogen-encoded proteases: global and selective inhibition
Autor: | Andrea Hodgson, Fengyi Wan |
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Rok vydání: | 2015 |
Předmět: |
0301 basic medicine
Proteases Protease Protein subunit medicine.medical_treatment Cell Virulence Biology Bioinformatics Microbiology Cell biology 03 medical and health sciences 030104 developmental biology medicine.anatomical_structure Immune system medicine Signal transduction Molecular Biology Gene |
Zdroj: | Molecular Microbiology. 99:439-452 |
ISSN: | 0950-382X |
Popis: | Pathogens have evolved a myriad of ways to abrogate and manipulate the host response to infections. Of the various mechanisms involved, pathogen-encoded and sometimes host-encoded proteases are an important category of virulence factors that cause robust changes on the host response by targeting key proteins along signaling cascades. The nuclear factor kappaB (NF-κB) signaling pathway is a crucial regulatory mechanism for the cell, controlling the expression of survival, immune and proliferation genes. Proteases from pathogens of almost all types have been demonstrated to target and cleave members of the NF-κB signaling pathway at nearly every level. This review provides discussion of proteases targeting the most abundant NF-κB subunit, p65, and the impact of protease-mediated p65 cleavage on the immune responses and survival of the infected host cell. After examining various examples of protease interference, it becomes evident that the cleavage fragments produced by pathogen-driven proteolytic processing should be further characterized to determine whether they have novel and unique functions within the cell. The selective targeting of p65 and its effect on gene transcription reveals unique mechanisms by which pathogens acutely alter their microenvironment, and further research may open new opportunities for novel therapeutics to combat pathogens. |
Databáze: | OpenAIRE |
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