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The first complete demonstration of a role for an Atg factor in autophagy in mammals using an ATG5 knockout mouse.
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Autophagy defends cells against invading group A Streptococcus
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••], this paper demonstrates the innate defense role of autophagy against bacterial pathogens. Although a typical extracellular pathogen (Streptococcus pyogenes) was used, once inside the host cells, the intracellular streptococci were eliminated by exceptionally large autophagosomes.
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••], this paper demonstrates the innate defense role of autophagy against bacterial pathogens. Although a typical extracellular pathogen (Streptococcus pyogenes) was used, once inside the host cells, the intracellular streptococci were eliminated by exceptionally large autophagosomes.
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••], this paper demonstrates the innate defense role of autophagy against bacterial pathogens. Shigella normally escapes from the phagosome into the cytosol. Autophagy was proved to be a cellular mechanism capable of eliminating from the cytosol mutated bacteria that lost their intracellular motility (i.e. their ability to polymerize actin and move rapidly on actin tails). In our interpretation, this could be an indication that the cytosolic motility of pathogens that escape from vacuoles into the cytosol might be a countermeasure deployed by bacteria to escape nascent autophagosomes.
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••], this paper demonstrates the innate defense role of autophagy against bacterial pathogens. Shigella normally escapes from the phagosome into the cytosol. Autophagy was proved to be a cellular mechanism capable of eliminating from the cytosol mutated bacteria that lost their intracellular motility (i.e. their ability to polymerize actin and move rapidly on actin tails). In our interpretation, this could be an indication that the cytosolic motility of pathogens that escape from vacuoles into the cytosol might be a countermeasure deployed by bacteria to escape nascent autophagosomes.
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••], this paper demonstrates the innate defense role of autophagy against bacterial pathogens. Pharmacologically, physiologically or immunologically induced autophagy was active in eliminating intraphagosomal mycobacteria. The immunological induction of autophagy was achieved by IFN-γ, through a process that included Irgm1 (LRG-47). Irgm1 is an immunity-related GTPasethat protects against M. tuberculosis with a previously unknown mode of action, which turned out to modulate autophagy.
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••], this paper demonstrates the innate defense role of autophagy against bacterial pathogens. Pharmacologically, physiologically or immunologically induced autophagy was active in eliminating intraphagosomal mycobacteria. The immunological induction of autophagy was achieved by IFN-γ, through a process that included Irgm1 (LRG-47). Irgm1 is an immunity-related GTPasethat protects against M. tuberculosis with a previously unknown mode of action, which turned out to modulate autophagy.
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The first publication demonstrating the role of macroautophagy in MHC II presentation of endogenously synthesized viral protein. Because the protein in question, EBNA1, was a viral product, this also implicated autophagy in adaptive immunity against intracellular pathogens.
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Paludan C., Schmid D., Landthaler M., Vockerodt M., Kube D., Tuschl T., and Munz C. Endogenous MHC class II processing of a viral nuclear antigen after autophagy. Science 307 (2005) 593-596. The first publication demonstrating the role of macroautophagy in MHC II presentation of endogenously synthesized viral protein. Because the protein in question, EBNA1, was a viral product, this also implicated autophagy in adaptive immunity against intracellular pathogens.
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A demonstration of the role of autophagy in endogenous MHC II class antigen processing and presentation. This study also presents a comprehensive analysis of MHC II bound peptides from cytoplasmic sources upon induction of autophagy.
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Dengjel J., Schoor O., Fischer R., Reich M., Kraus M., Muller M., Kreymborg K., Altenberend F., Brandenburg J., Kalbacher H., et al. Autophagy promotes MHC class II presentation of peptides from intracellular source proteins. Proc Natl Acad Sci USA 102 (2005) 7922-7927. A demonstration of the role of autophagy in endogenous MHC II class antigen processing and presentation. This study also presents a comprehensive analysis of MHC II bound peptides from cytoplasmic sources upon induction of autophagy.
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Crotzer V.L., and Blum J.S. Autophagy and intracellular surveillance: modulating MHC class II antigen presentation with stress. Proc Natl Acad Sci USA 102 (2005) 7779-7780
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Processing and presentation of HLA class I and II epitopes by dendritic cells after transfection with in vitro-transcribed MUC1 RNA
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Byfield M.P., Murray J.T., and Backer J.M. hVps34 is a nutrient-regulated lipid kinase required for activation of p70 S6 kinase. J Biol Chem 280 (2005) 33076-33082
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Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase
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Nobukuni T., Joaquin M., Roccio M., Dann S.G., Kim S.Y., Gulati P., Byfield M.P., Backer J.M., Natt F., Bos J.L., et al. Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase. Proc Natl Acad Sci USA 102 (2005) 14238-14243
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A superb study linking autophagy and apoptosis via Beclin-Bcl-2 interaction. This work is important for our understanding of the coordination between the two programmed cell death pathways, and also because it shows a central role of Beclin, a subunit of the PI3 kinase hVPS34 complex, in the regulation of autophagy.
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Pattingre S., Tassa A., Qu X., Garuti R., Liang X.H., Mizushima N., Packer M., Schneider M.D., and Levine B. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 122 (2005) 927-939. A superb study linking autophagy and apoptosis via Beclin-Bcl-2 interaction. This work is important for our understanding of the coordination between the two programmed cell death pathways, and also because it shows a central role of Beclin, a subunit of the PI3 kinase hVPS34 complex, in the regulation of autophagy.
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This study shows molecular details of the interactions between Beclin and hVPS34 (a PI3 kinase crucial for the execution stages of autophagy). It also demonstrates a specific role for Beclin in autophagy of mammalian cells and suggests that it might not take part in the generic endosomal-lysosomal pathway.
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Furuya T., Yu J., Byfield M., Pettingre S., and Levine B. The evolutionarily conserved domain of Beclin 1 is required for Vps34 binding, autophagy and tumor suppressor function. Autophagy 1 (2005) 46-52. This study shows molecular details of the interactions between Beclin and hVPS34 (a PI3 kinase crucial for the execution stages of autophagy). It also demonstrates a specific role for Beclin in autophagy of mammalian cells and suggests that it might not take part in the generic endosomal-lysosomal pathway.
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A study demonstrating a cell survival-promoting function of autophagy.
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Lum J.J., Bauer D.E., Kong M., Harris M.H., Li C., Lindsten T., and Thompson C.B. Growth factor regulation of autophagy and cell survival in the absence of apoptosis. Cell 120 (2005) 237-248. A study demonstrating a cell survival-promoting function of autophagy.
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A recent report extending a role for autophagy in clearing yet another intracellular bacterium.
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Cholesterol depletion in Mycobacterium avium-infected macrophages overcomes the block in phagosome maturation and leads to the reversible sequestration of viable mycobacteria in phagolysosome-derived autophagic vacuoles
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A recent report suggesting association of autophagy with another facultative intracellular opportunistic mycobacterial pathogen, M. avium, although autophagosomes apparently could not eliminate this microorganism. In this case, cholesterol manipulation was used, which might be related to the reported effects.
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Cell Microbiol
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A recent report highlighting the other side of autophagy, in its paradoxical role of supporting pathogen's replication in host cells. This reflects evolutionary adaptations by some viruses and, as shown by others, some obligate intracellular bacteria.
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A superb and comprehensive bioinformatics analysis of immunity-related GTPase (IRG)-encoding genes in mammals and lower vertebrates. This study uncovers the unexpectedly large number of Irg genes (22 complete genes and 2 pseudogenes) in the mouse genome, by far exceeding the previously studied six Irg members. Even more surprising, if not shocking, was the finding that the human genome encodes only three IRG genes.
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Bekpen C., Hunn J.P., Rohde C., Parvanova I., Guethlein L., Dunn D.M., Glowalla E., Leptin M., and Howard J.C. The interferon-inducible p47 (IRG) GTPases in vertebrates: loss of the cell autonomous resistance mechanism in the human lineage. Genome Biol 6 (2005) R92. A superb and comprehensive bioinformatics analysis of immunity-related GTPase (IRG)-encoding genes in mammals and lower vertebrates. This study uncovers the unexpectedly large number of Irg genes (22 complete genes and 2 pseudogenes) in the mouse genome, by far exceeding the previously studied six Irg members. Even more surprising, if not shocking, was the finding that the human genome encodes only three IRG genes.
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This work demonstrates the role of chaperone-mediated autophagy in MHC II presentation of endogenously synthesized cytosolic antigens.
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Deretic, V.1
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