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Inflammation plays a crucial role in AML progression, but excessive activation of cell-intrinsic inflammatory pathways can also trigger cell death. IRF2BP2 is a chromatin regulator implicated in AML pathogenesis, although its precise role in this disease is not fully understood. In this study, we demonstrate that IRF2BP2 interacts with the AP-1 heterodimer ATF7\/JDP2, which is involved in activating inflammatory pathways in AML cells. We show that IRF2BP2 is recruited by the ATF7\/JDP2 dimer to chromatin and counteracts its gene-activating function. Loss of IRF2BP2 leads to overactivation of inflammatory pathways, resulting in strongly reduced proliferation. Our research indicates that a precise equilibrium between activating and repressive transcriptional mechanisms creates a pro-oncogenic inflammatory environment in AML cells. The ATF7\/JDP2-IRF2BP2 regulatory axis is likely a key regulator of this process and may, therefore, represent a promising therapeutic vulnerability for AML. Thus, our study provides new insights into the molecular mechanisms underlying AML pathogenesis and identifies a potential therapeutic target for AML treatment.<\/jats:p>","DOI":"10.1093\/nar\/gkae437","type":"journal-article","created":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T02:09:03Z","timestamp":1715652543000},"page":"7590-7609","source":"Crossref","is-referenced-by-count":8,"title":["IRF2BP2 counteracts the ATF7\/JDP2 AP-1 heterodimer to prevent inflammatory overactivation in acute myeloid leukemia (AML) cells"],"prefix":"10.1093","volume":"52","author":[{"given":"Sabrina","family":"Fischer","sequence":"first","affiliation":[{"name":"Institute of Molecular Biology and Tumor Research (IMT), Philipps University of Marburg , Marburg\u00a035043 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa Marie","family":"Weber","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Tumor Research (IMT), Philipps University of Marburg , Marburg\u00a035043 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bastian","family":"Stielow","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Tumor Research (IMT), Philipps University of Marburg , Marburg\u00a035043 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Frech","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology, and Immunology, University Hospital Giessen and Marburg , Marburg\u00a035043 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Simon","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Tumor Research (IMT), Philipps University of Marburg , Marburg\u00a035043 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merle","family":"Geller","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Tumor 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Nist","sequence":"additional","affiliation":[{"name":"Genomics Core Facility, Institute of Molecular Oncology, Member of the German Center for Lung Research (DZL), Philipps University of Marburg , Marburg\u00a035043 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uta-Maria","family":"Bauer","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Tumor Research (IMT), Philipps University of Marburg , Marburg\u00a035043 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorsten","family":"Stiewe","sequence":"additional","affiliation":[{"name":"Genomics Core Facility, Institute of Molecular Oncology, Member of the German Center for Lung Research (DZL), Philipps University of Marburg , Marburg\u00a035043 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Neubauer","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology, and Immunology, University Hospital Giessen and Marburg , Marburg\u00a035043 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8549-637X","authenticated-orcid":false,"given":"Robert","family":"Liefke","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Tumor Research (IMT), Philipps University of Marburg , Marburg\u00a035043 , Germany"},{"name":"Department of Hematology, Oncology, and Immunology, University Hospital Giessen and Marburg , Marburg\u00a035043 , 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