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dc.contributor.authorCammarata-Mouchtouris, Alexandre
dc.contributor.authorNguyen, Xuan Hung
dc.contributor.authorAcker, Adrian
dc.contributor.authorBonnay, François
dc.contributor.authorGoto, Akira
dc.contributor.authorOrian, Amir
dc.contributor.authorFauvarque, Marie-Odile
dc.contributor.authorBoutros, Michael
dc.contributor.authorReichhart, Jean-Marc
dc.contributor.authorMatt, Nicolas
dc.date.accessioned2024-08-21T16:05:10Z
dc.date.available2024-08-21T16:05:10Z
dc.date.issued2020-04-27
dc.identifier.urihttps://vinspace.edu.vn/handle/VIN/215
dc.description.abstractThe Immune Deficiency (IMD) pathway in Drosophila melanogaster is activated in response to microbial challenges, particularly by Gram-negative bacteria, to initiate the innate immune response. To elucidate the nuclear factor κB (NF-κB) signaling pathway, we conducted an in vitro RNA interference (RNAi) screen targeting E3 ubiquitin ligases and identified the HECT-type E3 ubiquitin ligase Hyperplastic discs (Hyd) as a novel component of the IMD pathway. We discovered that Hyd mediates Lys63 (K63)-linked polyubiquitination of the NF-κB cofactor Akirin, which is crucial for Akirin’s efficient binding to the NF-κB transcription factor Relish. This Hyd-dependent interaction is essential for the transcription of immunity-related genes activated by both Relish and Akirin but is not required for genes dependent solely on Relish. Consequently, Hyd plays a critical role in NF-κB transcriptional selectivity downstream of the IMD pathway. Drosophila mutants lacking Akirin or Hyd fail to express the full range of immune-induced antimicrobial peptides and exhibit heightened susceptibility to immune challenges. Furthermore, we found that UBR5, the mammalian homolog of Hyd, is also necessary for NF-κB-mediated activation of Interleukin 6 (IL6) transcription in response to LPS or IL-1β in human cell cultures. Our findings establish a direct link between an E3 ubiquitin ligase and the activation of immune effector genes, advancing our understanding of ubiquitination in inflammation and highlighting a potential target for controlling inflammatory diseases.en_US
dc.language.isoen_USen_US
dc.titleHyd ubiquitinates the NF-κB co-factor Akirin to operate an effective immune response in Drosophilaen_US
dc.typeArticleen_US


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