The Brucella effector protein BspF crotonylates TRIM38 to inhibit NF-κB and MAPK signaling pathway. | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The Brucella effector protein BspF crotonylates TRIM38 to inhibit NF-κB and MAPK signaling pathway. Jinying Zhu, Sijiao Wu, Yukai Xing, Yuzhuo Li, Yuqi Wang, Jingbo Gao, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4464860/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Brucellosis is caused by Brucella , which is a highly prevalent intracellular parasite. Type IV secretion system(T4SS) is an important virulence factor of Brucella . T4SS secretes 16 effector proteins, which affect the intracellular transport of Brucella -containing vacuole and regulate the host immune response, helping Brucella to survive and replicate in host cells. In our previous crotonylation proteomics data of HEK-293T cell proteintriggered by BspF, we found BspF crotonylated on TRIM38, which is an important modulator in the pathways of inflammation, and the crotonylation site is K142. Therefore, it is speculated that BspF may be involved in the regulation of host inflammatory response during Brucella infection. In this study, we found BspF-mediated TRIM38K142 crotonylation promotes the ubiquitination of Tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6), leading to the degradation of TRAF6, thereby inhibiting the transduction of NF-κB, p38 MAPK and JNK MAPK signaling pathways and inhibits the secretion of pro-inflammatory factors IL-1β, IL-6 and IL-8, which finally helps Brucella to promote intracellular survival. This study provides a new theoretical basis for Brucella to achieve intracellular survival by regulating host innate immunity through T4SS, and provides an important reference for the study of non-histone crotonylation. Brucella BspF Crotonylation NF-κB MAPK Full Text Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4464860","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":315587435,"identity":"7a673758-cdb4-43f4-ae06-2c27e167934b","order_by":0,"name":"Jinying Zhu","email":"","orcid":"","institution":"Shenyang Agricultural University","correspondingAuthor":false,"prefix":"","firstName":"Jinying","middleName":"","lastName":"Zhu","suffix":""},{"id":315587436,"identity":"1cfa489d-a1a0-45f3-acd9-b72ea8dc788d","order_by":1,"name":"Sijiao Wu","email":"","orcid":"","institution":"Shenyang Agricultural 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