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Enteric pathogens deploy cell cycle inhibiting factors to block the bactericidal activity of Perforin-2.
- Source :
-
ELife [Elife] 2015 Sep 29; Vol. 4. Date of Electronic Publication: 2015 Sep 29. - Publication Year :
- 2015
-
Abstract
- Perforin-2 (MPEG1) is an effector of the innate immune system that limits the proliferation and spread of medically relevant Gram-negative, -positive, and acid fast bacteria. We show here that a cullin-RING E3 ubiquitin ligase (CRL) complex containing cullin-1 and βTrCP monoubiquitylates Perforin-2 in response to pathogen associated molecular patterns such as LPS. Ubiquitylation triggers a rapid redistribution of Perforin-2 and is essential for its bactericidal activity. Enteric pathogens such as Yersinia pseudotuberculosis and enteropathogenic Escherichia coli disarm host cells by injecting cell cycle inhibiting factors (Cifs) into mammalian cells to deamidate the ubiquitin-like protein NEDD8. Because CRL activity is dependent upon NEDD8, Cif blocks ubiquitin dependent trafficking of Perforin-2 and thus, its bactericidal activity. Collectively, these studies further underscore the biological significance of Perforin-2 and elucidate critical molecular events that culminate in Perforin-2-dependent killing of both intracellular and extracellular, cell-adherent bacteria.
- Subjects :
- Animals
Cell Line
Cullin Proteins metabolism
Enteropathogenic Escherichia coli physiology
Humans
NEDD8 Protein
Pore Forming Cytotoxic Proteins antagonists & inhibitors
Ubiquitins antagonists & inhibitors
Yersinia pseudotuberculosis physiology
Cell Cycle drug effects
Enteropathogenic Escherichia coli immunology
Host-Pathogen Interactions
Microbial Viability
Pore Forming Cytotoxic Proteins toxicity
Virulence Factors metabolism
Yersinia pseudotuberculosis immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2050-084X
- Volume :
- 4
- Database :
- MEDLINE
- Journal :
- ELife
- Publication Type :
- Academic Journal
- Accession number :
- 26418746
- Full Text :
- https://doi.org/10.7554/eLife.06505