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Remarkably, Brucella sp. genomes encode a protein, named TcpB, that bears significant homology with mammalian Toll\/IL-1 receptor domains and whose expression causes degradation of the phosphorylated, signal competent form of the adapter MyD88-adapter\u2013like (MAL). This effect of TcpB is mediated through its box 1 region and has no effect on other TLR adapter proteins such as MyD88 or TIR-domain containing adapter protein-inducing IFN\u03b2. TcpB also does not affect a mutant, signal-incompetent form of MAL that cannot be phosphorylated. Interestingly, the presence of TcpB leads to enhanced polyubiqitination of MAL, which is likely responsible for its accelerated degradation. A Brucella abortus mutant lacking TcpB fails to reduce levels of MAL in infected macrophages. Therefore, TcpB represents a unique pathogen-derived molecule that suppresses host innate-immune responses by specifically targeting an individual adapter molecule in the TLR signaling pathway for degradation.<\/jats:p>","DOI":"10.4049\/jimmunol.0902008","type":"journal-article","created":{"date-parts":[[2009,12,14]],"date-time":"2009-12-14T22:19:26Z","timestamp":1260829166000},"page":"956-964","source":"Crossref","is-referenced-by-count":113,"title":["Subversion of Innate Immune Responses by\n                    <i>Brucella<\/i>\n                    through the Targeted Degradation of the TLR Signaling Adapter, MAL"],"prefix":"10.1093","volume":"184","author":[{"given":"Dola","family":"Sengupta","sequence":"first","affiliation":[{"name":"Department of Immunobiology"},{"name":"Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Koblansky","sequence":"additional","affiliation":[{"name":"Department of Immunobiology"},{"name":"Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine , New Haven, CT 06520"},{"name":"Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University , New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Gaines","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, East Carolina University School of Medicine , Greenville, NC 27834"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, East Carolina University School of Medicine , Greenville, NC 27834"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A Phillip","family":"West","sequence":"additional","affiliation":[{"name":"Department of Immunobiology"},{"name":"Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dekai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Immunobiology"},{"name":"Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tak","family":"Nishikawa","sequence":"additional","affiliation":[{"name":"Department of Immunobiology"},{"name":"Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Gyoo","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Immunobiology"},{"name":"Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine , New Haven, CT 06520"},{"name":"Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University , New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"II","given":"R Martin","family":"Roop","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, East Carolina University School of Medicine , Greenville, NC 27834"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sankar","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Department of Immunobiology"},{"name":"Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine , New Haven, CT 06520"},{"name":"Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University , New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,27]]},"reference":[{"key":"2026012808101836200_r1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.coi.2005.11.012","article-title":"How Toll-like receptors signal: what we know and what we don\u2019t know.","volume":"18","author":"O\u2019Neill","year":"2006","journal-title":"Curr. 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