{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:04:28Z","timestamp":1791295468806,"version":"4.1.0"},"reference-count":30,"publisher":"Rockefeller University Press","issue":"10","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,11,21]]},"abstract":"<jats:p>The bacterial pathogens of the genus Yersinia, the causative agents of plague, septicemia, and gastrointestinal syndromes, use a type III secretion system to inject virulence factors into host target cells. One virulence factor, YopJ, is essential for the death of infected macrophages and can block host proinflammatory responses by inhibiting both the nuclear factor \u03baB (NF-\u03baB) and mitogen-activated protein kinase pathways, which might be important for evasion of the host immune response and aid in establishing a systemic infection. Here, we show that YopJ is a promiscuous deubiquitinating enzyme that negatively regulates signaling by removing ubiquitin moieties from critical proteins, such as TRAF2, TRAF6, and I\u03baB\u03b1. In contrast to the cylindromatosis tumor suppressor CYLD, which attenuates NF-\u03baB signaling by selectively removing K63-linked polyubiquitin chains that activate I\u03baB kinase, YopJ also cleaves K48-linked chains and thereby inhibits proteasomal degradation of I\u03baB\u03b1. YopJ, but not a catalytically inactive YopJ mutant, promoted deubiquitination of cellular proteins and cleaved both K48- and K63-linked polyubiquitin. Moreover, an in vitro assay was established to demonstrate directly the deubiquitinating activity of purified YopJ.<\/jats:p>","DOI":"10.1084\/jem.20051194","type":"journal-article","created":{"date-parts":[[2005,11,21]],"date-time":"2005-11-21T19:19:18Z","timestamp":1132600758000},"page":"1327-1332","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":191,"title":["<i>Yersinia<\/i>\n                    virulence factor YopJ acts as a deubiquitinase to inhibit NF-\u03baB activation"],"prefix":"10.1084","volume":"202","author":[{"given":"Honglin","family":"Zhou","sequence":"first","affiliation":[{"name":"1Molecular Oncology Department, Genentech, Inc., San Francisco, CA 94080"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise M.","family":"Monack","sequence":"additional","affiliation":[{"name":"3Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiko","family":"Kayagaki","sequence":"additional","affiliation":[{"name":"1Molecular Oncology Department, Genentech, Inc., San Francisco, CA 94080"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Wertz","sequence":"additional","affiliation":[{"name":"1Molecular Oncology Department, Genentech, Inc., San Francisco, CA 94080"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianpin","family":"Yin","sequence":"additional","affiliation":[{"name":"2Protein Engineering Department, Genentech, Inc., San Francisco, CA 94080"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beni","family":"Wolf","sequence":"additional","affiliation":[{"name":"1Molecular Oncology Department, Genentech, Inc., San Francisco, CA 94080"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishva M.","family":"Dixit","sequence":"additional","affiliation":[{"name":"1Molecular Oncology Department, Genentech, Inc., San Francisco, CA 94080"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2005,11,21]]},"reference":[{"key":"2023072513061294500_BIB1","doi-asserted-by":"crossref","first-page":"8778","DOI":"10.1073\/pnas.97.16.8778","volume":"97","year":"2000","journal-title":"Proc. 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