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dc.contributor.authorPaquette, Nicholas Paul
dc.contributor.authorBroemer, Meike
dc.contributor.authorAggarwal, Kamna
dc.contributor.authorChen, Li
dc.contributor.authorHusson, Marie
dc.contributor.authorErturk Hasdemir, Deniz
dc.contributor.authorReichhart, Jean-Marc
dc.contributor.authorMeier, Pascal
dc.contributor.authorSilverman, Neal S.
dc.date2022-08-11T08:09:10.000
dc.date.accessioned2022-08-23T16:20:00Z
dc.date.available2022-08-23T16:20:00Z
dc.date.issued2010-01-28
dc.date.submitted2010-02-03
dc.identifier.citationNicholas Paquette, Meike Broemer, Kamna Aggarwal, Li Chen, Marie Husson, Deniz Erturk-Hasdemir, Jean-Marc Reichhart, Pascal Meier, Neal Silverman. Caspase-Mediated Cleavage, IAP Binding, and Ubiquitination: Linking Three Mechanisms Crucial for Drosophila NF-[kappa]B Signaling. Molecular Cell, Volume 37, Issue 2, 29 January 2010, Pages 172-182. <a href="http://dx.doi.org/10.1016/j.molcel.2009.12.036">Link to article on publisher's website</a>
dc.identifier.doi10.1016/j.molcel.2009.12.036
dc.identifier.pmid20122400
dc.identifier.urihttp://hdl.handle.net/20.500.14038/35185
dc.description.abstractInnate immune responses are critical for the immediate protection against microbial infection. In Drosophila, infection leads to the rapid and robust production of antimicrobial peptides through two NF-κB signaling pathways—IMD and Toll. The IMD pathway is triggered by DAP-type peptidoglycan, common to most Gram-negative bacteria. Signaling downstream from the peptidoglycan receptors is thought to involve K63 ubiquitination and caspase-mediated cleavage, but the molecular mechanisms remain obscure. We now show that PGN stimulation causes caspase-mediated cleavage of the imd protein, exposing a highly conserved IAP-binding motif (IBM) at its neo-N terminus. A functional IBM is required for the association of cleaved IMD with the ubiquitin E3-ligase DIAP2. Through its association with DIAP2, IMD is rapidly conjugated with K63-linked polyubiquitin chains. These results mechanistically connect caspase-mediated cleavage and K63 ubiquitination in immune-induced NF-κB signaling.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=20122400&dopt=Abstract">Link to article in PubMed</a>
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2819219/pdf/nihms172103.pdf
dc.subjectImmunity, Innate
dc.subjectDrosophila
dc.subjectIntracellular Signaling Peptides and Proteins
dc.subjectSignal Transduction
dc.subjectDNA Cleavage
dc.subjectCaspases
dc.subjectInhibitor of Apoptosis Proteins
dc.subjectUbiquitination
dc.subjectImmunology and Infectious Disease
dc.titleCaspase-Mediated Cleavage, IAP Binding, and Ubiquitination: Linking Three Mechanisms Crucial for Drosophila NF-κB Signaling
dc.typeJournal Article
dc.source.journaltitleMolecular Cell
dc.source.volume37
dc.source.issue2
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/infdis_pp/41
dc.identifier.contextkey1130377
html.description.abstract<p>Innate immune responses are critical for the immediate protection against microbial infection. In Drosophila, infection leads to the rapid and robust production of antimicrobial peptides through two NF-κB signaling pathways—IMD and Toll. The IMD pathway is triggered by DAP-type peptidoglycan, common to most Gram-negative bacteria. Signaling downstream from the peptidoglycan receptors is thought to involve K63 ubiquitination and caspase-mediated cleavage, but the molecular mechanisms remain obscure. We now show that PGN stimulation causes caspase-mediated cleavage of the imd protein, exposing a highly conserved IAP-binding motif (IBM) at its neo-N terminus. A functional IBM is required for the association of cleaved IMD with the ubiquitin E3-ligase DIAP2. Through its association with DIAP2, IMD is rapidly conjugated with K63-linked polyubiquitin chains. These results mechanistically connect caspase-mediated cleavage and K63 ubiquitination in immune-induced NF-κB signaling.</p>
dc.identifier.submissionpathinfdis_pp/41
dc.contributor.departmentDepartment of Medicine, Division of Infectious Diseases and Immunology
dc.source.pages172-182


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