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dc.creatorwang, luqiao
dc.creatorFu, Hangfei
dc.creatorNanayakkara, Gayani
dc.creatorLi, Yafeng
dc.creatorShao, Ying
dc.creatorJohnson, Candice
dc.creatorCheng, Jiali
dc.creatorYang, William Y.
dc.creatorYang, Fan
dc.creatorLavallee, Muriel
dc.creatorXu, Yanjie
dc.creatorCheng, Xiaoshu
dc.creatorXi, Hang
dc.creatorYi, Jonathan
dc.creatorYu, Jun
dc.creatorChoi, Eric T.
dc.creatorWang, Hong
dc.creatorYang, Xiaofeng
dc.date.accessioned2023-06-22T15:11:28Z
dc.date.available2023-06-22T15:11:28Z
dc.date.issued2016-11-14
dc.identifier.citationWang, L., Fu, H., Nanayakkara, G. et al. Novel extracellular and nuclear caspase-1 and inflammasomes propagate inflammation and regulate gene expression: a comprehensive database mining study. J Hematol Oncol 9, 122 (2016). https://doi.org/10.1186/s13045-016-0351-5
dc.identifier.issn1756-8722
dc.identifier.doihttp://dx.doi.org/10.34944/dspace/8711
dc.identifier.urihttp://hdl.handle.net/20.500.12613/8747
dc.description.abstractBackground: Caspase-1 is present in the cytosol as an inactive zymogen and requires the protein complexes named “inflammasomes” for proteolytic activation. However, it remains unclear whether the proteolytic activity of caspase-1 is confined only to the cytosol where inflammasomes are assembled to convert inactive pro-caspase-1 to active caspase-1. Methods: We conducted meticulous data analysis method s on proteomic, protein interaction, protein intracellular localization, and gene expressions of 114 experimentally identified caspase-1 substrates and 38 caspase-1 interaction proteins in normal physiological conditions and in various pathologies. Results: We made the following important findings: (1) Caspase-1 substrates and interaction proteins are localized in various intracellular organelles including nucleus and secreted extracellularly; (2) Caspase-1 may get activated in situ in the nucleus in response to intra-nuclear danger signals; (3) Caspase-1 cleaves its substrates in exocytotic secretory pathways including exosomes to propagate inflammation to neighboring and remote cells; (4) Most of caspase-1 substrates are upregulated in coronary artery disease regardless of their subcellular localization but the majority of metabolic diseases cause no significant expression changes in caspase-1 nuclear substrates; and (5) In coronary artery disease, majority of upregulated caspase-1 extracellular substrate-related pathways are involved in induction of inflammation; and in contrast, upregulated caspase-1 nuclear substrate-related pathways are more involved in regulating cell death and chromatin regulation. Conclusions: Our identification of novel caspase-1 trafficking sites, nuclear and extracellular inflammasomes, and extracellular caspase-1-based inflammation propagation model provides a list of targets for the future development of new therapeutics to treat cardiovascular diseases, inflammatory diseases, and inflammatory cancers.
dc.format.extent18 pages
dc.languageEnglish
dc.language.isoeng
dc.relation.ispartofFaculty/ Researcher Works
dc.relation.haspartJournal of Hematology & Oncology, Vol. 9
dc.relation.isreferencedbyBMC
dc.rightsAttribution CC BY
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectCaspase-1
dc.subjectTrafficking
dc.subjectNuclear gene regulation
dc.subjectInflammation propagation
dc.subjectExosome
dc.titleNovel extracellular and nuclear caspase-1 and inflammasomes propagate inflammation and regulate gene expression: a comprehensive database mining study
dc.typeText
dc.type.genreJournal article
dc.contributor.groupCenters for Metabolic Disease Research (Temple University)
dc.contributor.groupCardiovascular Research and Thrombosis Research (Temple University)
dc.description.departmentPharmacology
dc.description.departmentSurgery
dc.description.departmentPhysiology
dc.relation.doihttps://doi.org/10.1186/s13045-016-0351-5
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
dc.description.schoolcollegeLewis Katz School of Medicine
dc.creator.orcidWang, Luqiao|0000-0003-0263-9492
dc.creator.orcidShao|0000-0001-5879-0154
dc.creator.orcidWang, Hong|0000-0001-6258-4070
dc.creator.orcidYang, Xiaofeng|0000-0002-6854-6195
dc.temple.creatorWang, Luqiao
dc.temple.creatorFu, Hangfei
dc.temple.creatorNanayakkara, Gayani
dc.temple.creatorLi, Yafeng
dc.temple.creatorShao, Ying
dc.temple.creatorJohnson, Candice
dc.temple.creatorCheng, Jiali
dc.temple.creatorYang, William Y.
dc.temple.creatorYang, Fan
dc.temple.creatorLavallee, Muriel
dc.temple.creatorXu, Yanjie
dc.temple.creatorXi, Hang
dc.temple.creatorYi, Jonathan
dc.temple.creatorYu, Jun
dc.temple.creatorChoi, Eric T.
dc.temple.creatorWang, Hong
dc.temple.creatorYang, Xiao-Feng
refterms.dateFOA2023-06-22T15:11:28Z


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