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Cathepsin B modulates lysosomal biogenesis and host defense against Francisella novicida infection
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Qi, Xiaopeng | - |
dc.contributor.author | Man, Si Ming | - |
dc.contributor.author | Malireddi, R. K. Subbarao | - |
dc.contributor.author | Karki, Rajendra | - |
dc.contributor.author | Lupfer, Christopher | - |
dc.contributor.author | Gurung, Prajwal | - |
dc.contributor.author | Neale, Geoffrey | - |
dc.contributor.author | Guy, Clifford S. | - |
dc.contributor.author | Lamkanfi, Mohamed | - |
dc.contributor.author | Kanneganti, Thirumala-Devi | - |
dc.date.accessioned | 2024-05-16T01:58:54Z | - |
dc.date.available | 2024-05-16T01:58:54Z | - |
dc.date.created | 2023-05-08 | - |
dc.date.created | 2023-05-08 | - |
dc.date.issued | 2016-09 | - |
dc.identifier.citation | Journal of Experimental Medicine, Vol.213 No.10, pp.2081-2097 | - |
dc.identifier.issn | 0022-1007 | - |
dc.identifier.uri | https://hdl.handle.net/10371/203048 | - |
dc.description.abstract | Lysosomal cathepsins regulate an exquisite range of biological functions, and their deregulation is associated with inflammatory, metabolic, and degenerative diseases in humans. In this study, we identified a key cell-intrinsic role for cathepsin B as a negative feedback regulator of lysosomal biogenesis and autophagy. Mice and macrophages lacking cathepsin B activity had increased resistance to the cytosolic bacterial pathogen Francisella novicida. Genetic deletion or pharmacological inhibition of cathepsin B down-regulated mechanistic target of rapamycin activity and prevented cleavage of the lysosomal calcium channel TRP ML1. These events drove transcription of lysosomal and autophagy genes via transcription factor EB, which increased lysosomal biogenesis and activation of autophagy initiation kinase ULK1 for clearance of the bacteria. Our results identified a fundamental biological function of cathepsin B in providing a checkpoint for homeostatic maintenance of lysosome populations and basic recycling functions in the cell. | - |
dc.language | 영어 | - |
dc.publisher | Rockefeller University Press | - |
dc.title | Cathepsin B modulates lysosomal biogenesis and host defense against Francisella novicida infection | - |
dc.type | Article | - |
dc.identifier.doi | 10.1084/jem.20151938 | - |
dc.citation.journaltitle | Journal of Experimental Medicine | - |
dc.identifier.wosid | 000384107700011 | - |
dc.identifier.scopusid | 2-s2.0-84992192230 | - |
dc.citation.endpage | 2097 | - |
dc.citation.number | 10 | - |
dc.citation.startpage | 2081 | - |
dc.citation.volume | 213 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Karki, Rajendra | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | AIM2 INFLAMMASOME | - |
dc.subject.keywordPlus | INNATE IMMUNITY | - |
dc.subject.keywordPlus | CELL-DEATH | - |
dc.subject.keywordPlus | TRYPSINOGEN ACTIVATION | - |
dc.subject.keywordPlus | NLRP3 INFLAMMASOMES | - |
dc.subject.keywordPlus | REGULATES AUTOPHAGY | - |
dc.subject.keywordPlus | SIGNALING PATHWAYS | - |
dc.subject.keywordPlus | CYTOSOLIC BACTERIA | - |
dc.subject.keywordPlus | HUMAN MACROPHAGES | - |
dc.subject.keywordPlus | DEFICIENT MICE | - |
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