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Post‐translational modifications of host proteins in pathogen defense (98.3)
Author(s) -
Xavier Ramnik
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.98.3
Subject(s) - autophagy , microbiology and biotechnology , biology , vacuole , atg8 , intracellular parasite , ubiquitin , bag3 , autophagosome , organelle , cytoplasm , intracellular , biochemistry , gene , apoptosis
Autophagy is a cellular disposal system that directs cytoplasmic cargo into lysosomes for proteolytic degradation. In addition to recycling biomass such as organelles, autophagy serves to capture and kill intracellular pathogens, thus representing a central mechanism of host defense that is evolutionarily conserved from plants to mammals, emerging evidence highlights the critical role of autophagy in host defense against a broad range of bacteria, which collectively represent one of the most medically important groups of human pathogens. Understanding how cells select and sort pathogens into the autophagic pathway without destroying important cellular components is a major question in the field. Using integrative genomics, we have previously identified FNBP1L (formin binding protein 1‐like) and LRSAM1 as essential for autophagy of S. Typhimurium. FNBP1L contains an F‐BAR domain, which is typically involved in membrane bending and linking membranes with the cytoskeleton. Although FNBPL1 is dispensable for classical forms of autophagy induced by serum starvation or rapamycin, FNBP1L expression serves to restrict the growth of S. Typhimurium through the antibacterial autophagy pathway. LRSAM1 functions as a human antibacterial sensor protein that both interacts with autophagic machinery and mediates target selection for antibacterial autophagy. LRSAM1 is a target‐specific E3 ligase responsible for the ubiquitination of intracellular S . Typhimurium and thus meditates a key step in the induction of the major anti‐ Salmonella autophagy pathway. We will present data based on screening >3000 candidate genes in the autophagic response to S. Typhimurium . The initial set was selected based on their identification as: (1) common genetic variants associated with Crohn’s disease and ulcerative colitis; (2) genes associated with the selective autophagic targeting of viruses/bacteria; (3) E3 ubiquitin ligases; and (4) genes identified through proteomic protein‐protein interaction analysis as key regulators of the autophagy network