University of Massachusetts, Departments of Medicine details research in plague
2007 NOV 13 -- A report, 'YopJ targets TRAF proteins to inhibit TLR-mediated NF-kappaB, MAPK and IRF3 signal transduction,' is newly published data in Cellular Microbiology. "The Yersinia pestis virulence factor YopJ is a potent inhibitor of the NF-kappaB and MAPK signalling pathways, however, its molecular mechanism and relevance to pathogenesis are the subject of much debate. In this report, we characterize the effects of this type III effector protein on bone fide signalling events downstream of Toll-like receptors (TLRs), critical sensors in innate immunity," scientists writing in the journal Cellular Microbiology report. "YopJ inhibited TLR-mediated NF-kappaB and MAP kinase activation, as suggested by previous studies. In addition, induction of the TLR-mediated interferon response was blocked by YopJ, indicating that YopJ also inhibits IRF3 signalling. Examination of the NF-kappaB signalling pathway in detail suggested that YopJ acts at the level of TAK1 (MAP3K7) activation. Further studies revealed a YopJ-dependent decrease in the ubiquitination of TRAF3 and TRAF6. These data support the hypothesis that YopJ is a deubiquitinating protease that acts on TRAF proteins to prevent or remove the K63-polymerized ubiquitin conjugates required for signal transduction," wrote C.R. Sweet and colleagues, University of Massachusetts, Departments of Medicine. The researchers concluded: "Our data do not directly address the alternative hypothesis that YopJ is an acetyltransferase that acts on the activation loop of IKK and MKK proteins, but support the conclusion that the critical function of YopJ is to deubiquinate TRAF proteins." Sweet and colleagues published their study in Cellular Microbiology (YopJ targets TRAF proteins to inhibit TLR-mediated NF-kappaB, MAPK and IRF3 signal transduction. Cellular Microbiology, 2007;9(11):2700-15). Additional information can be obtained by contacting C.R. Sweet, University of Massachusetts Medical School, University of Massachusetts Medical School, Departments of Medicine, Worcester, MA 01605 USA.. The publisher of the journal Cellular Microbiology can be contacted at: Blackwell Publishing Ltd., 9600 Garsington Rd., Oxford OX4 2DG, Oxon, England. Keywords: United States, Worcester, Bacteriology, Bubonic Plague, Cellular, Microbiology, Yersinia Pestis. This article was prepared by Health Risk Factor Week editors from staff and other reports. Copyright 2007, Health Risk Factor Week via NewsRx.com.
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