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Infectious agents such as Salmonella Typhimurium (STm), which causes gastroenteritis, utilize the PTM mechanism SUMOylation to hijack the host cell. STm suppresses host SUMO pathway genes UBC9 (also known as UBE2I) and PIAS1 to perturb SUMOylation for an efficient infection. In the present study, the regulation of SUMO pathway genes during STm infection was investigated. A direct binding of c-Fos (encoded by FOS), a component of activator protein-1 (AP-1), to promoters of both UBC9 and PIAS1 was observed. Experimental perturbation of c-Fos led to changes in the expression of both UBC9 and PIAS1. STm infection of fibroblasts with SUMOylation-deficient c-Fos (c-FOS-KOSUMO-def-FOS) resulted in uncontrolled activation of target genes, leading to massive immune activation. Infection of c-FOS-KOSUMO-def-FOS cells favored STm replication, indicating misdirected immune mechanisms. Finally, chromatin immunoprecipitation assays confirmed a context-dependent differential binding and release of AP-1 to and from target genes due to its phosphorylation and SUMOylation, respectively. Overall, our data point towards the existence of a bidirectional cross-talk between c-Fos and the SUMO pathway and highlight their importance in AP-1 function in STm infection and beyond.<\/jats:p>\n                  <jats:p>This article has an associated First Person interview with the first author of the paper.<\/jats:p>","DOI":"10.1242\/jcs.260096","type":"journal-article","created":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T04:43:21Z","timestamp":1659069801000},"source":"Crossref","is-referenced-by-count":6,"title":["Bidirectional regulation between AP-1 and SUMOylation pathway genes modulates inflammatory signaling during\n                    <i>Salmonella<\/i>\n                    infection"],"prefix":"10.1242","volume":"135","author":[{"given":"Pharvendra","family":"Kumar","sequence":"first","affiliation":[{"name":"Regional Centre for Biotechnology, 1 3rd milestone Gurugram-Faridabad Expressway, Faridabad 121001 , India"},{"name":"Kalinga Institute of Industrial Technology 2 , Bhubaneswar , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amarendranath","family":"Soory","sequence":"additional","affiliation":[{"name":"Indian Institute of Science Education and Research 3 , Pune 411008 , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salman Ahmad","family":"Mustfa","sequence":"additional","affiliation":[{"name":"King's College London 4 , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dipanka Tanu","family":"Sarmah","sequence":"additional","affiliation":[{"name":"Translational Health Science and Technology Institute 5 , 3rd milestone Gurugram-Faridabad Expressway, Faridabad 121001 , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Himadri","family":"Devvanshi","sequence":"additional","affiliation":[{"name":"Translational Health Science and Technology Institute 5 , 3rd milestone Gurugram-Faridabad Expressway, Faridabad 121001 , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samrat","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"Translational Health Science and Technology Institute 5 , 3rd milestone Gurugram-Faridabad Expressway, Faridabad 121001 , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Bossis","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique Mol\u00e9culaire de Montpellier (IGMM), University Montpellier, CNRS, 34293 6 Montpellier , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7615-3140","authenticated-orcid":false,"given":"Girish S.","family":"Ratnaparkhi","sequence":"additional","affiliation":[{"name":"Indian Institute of Science Education and Research 3 , Pune 411008 , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9381-1213","authenticated-orcid":false,"given":"Chittur V.","family":"Srikanth","sequence":"additional","affiliation":[{"name":"Regional Centre for Biotechnology, 1 3rd milestone Gurugram-Faridabad Expressway, Faridabad 121001 , India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2022,8,19]]},"reference":[{"key":"2022082313284993600_JCS260096C1","doi-asserted-by":"publisher","first-page":"7563","DOI":"10.1038\/sj.onc.1204880","article-title":"Identification of a C-terminal tripeptide motif involved in the control of rapid proteasomal degradation of c-Fos proto-oncoprotein during the G0-to-S phase transition","volume":"20","author":"Acquaviva","year":"2001","journal-title":"Oncogene"},{"key":"2022082313284993600_JCS260096C2","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1186\/s12918-018-0600-z","article-title":"Extracting proteins involved in disease progression using temporally connected networks","volume":"12","author":"Anand","year":"2018","journal-title":"BMC Syst. 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