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However, the molecular function of UGPase in <jats:italic>Brucella<\/jats:italic> is still unknown.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In this study, the ubiquitination modification of host immune-related protein in cells infected with UGPase-deleted or wild-type <jats:italic>Brucella<\/jats:italic> was analyzed using ubiquitination proteomics technology. The ubiquitination modification level and type of NF-\u03baB Essential Modulator (NEMO or Ikbkg), a molecule necessary for NF-\u03baB signal activation, was evaluated using Coimmunoprecipitation, Western blot, and dual-Luciferase Assay. We found 80 ubiquitin proteins were upregulated and 203 ubiquitin proteins were downregulated in cells infected with <jats:italic>B. melitensis<\/jats:italic> 16\u00a0M compared with those of <jats:italic>B. melitensis<\/jats:italic> UGPase-deleted strain (16\u00a0M-UGPase<jats:sup>\u2212<\/jats:sup>). Moreover, the ubiquitin-modified proteins were mostly enriched in the categories of regulation of kinase\/NF-\u03baB signaling and response to a bacterium, suggesting <jats:italic>Brucella<\/jats:italic> UGPase inhibits ubiquitin modification of related proteins in the host NF-\u03baB signaling pathway. Further analysis showed that the ubiquitination levels of NEMO K63 (K63-Ub) and Met1 (Met1-Ub) were significantly increased in the 16\u00a0M-UGPase<jats:sup>\u2212<\/jats:sup>-infected cells compared with that of the 16\u00a0M-infected cells, further confirming that the ubiquitination levels of NF-\u03baB signaling-related proteins were regulated by the bacterial UGPase. Besides, the expression level of I\u03baB\u03b1 was decreased, but the level of p-P65 was significantly increased in the 16\u00a0M-UGPase<jats:sup>\u2212<\/jats:sup>-infected cells compared with that of the 16\u00a0M- and mock-infected cells, demonstrating that <jats:italic>B. melitensis<\/jats:italic> UGPase can significantly inhibit the degradation of I\u03baB\u03b1 and the phosphorylation of p65, and thus suppressing the NF-\u03baB pathway.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The results of this study showed that <jats:italic>Brucella melitensis<\/jats:italic> UGPase inhibits the activation of NF-\u03baB by modulating the ubiquitination of NEMO, which will provide a new scientific basis for the study of immune mechanisms induced by <jats:italic>Brucella<\/jats:italic>.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12917-021-02993-9","type":"journal-article","created":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T11:02:53Z","timestamp":1630321373000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Brucella melitensis UGPase inhibits the activation of NF-\u03baB by modulating the ubiquitination of NEMO"],"prefix":"10.1186","volume":"17","author":[{"given":"Yucheng","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoyang","family":"Bu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuening","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianjiang","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sen","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shipeng","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinglong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linzhu","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanling","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,30]]},"reference":[{"issue":"1\u20134","key":"2993_CR1","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1016\/S0378-1135(02)00255-9","volume":"90","author":"GG Schurig","year":"2002","unstructured":"Schurig GG, Sriranganathan N, Corbel MJ. 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