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Keywords {🔍}

caspase, substrates, proteins, pubmed, article, google, scholar, nuclear, interaction, cas, nucleus, protein, inflammasome, cell, table, disease, inflammasomes, inflammation, upregulated, subcellular, extracellular, expression, localization, localized, activated, cells, central, data, database, cytosol, intracellular, pathways, coronary, procaspase, experimentally, inflammatory, active, response, analysis, including, activation, artery, model, cytosolic, extracellularly, danger, death, found, yang, identified,

Topics {✒️}

uniprotkb/swiss-prot location database exosome-mediated inflammasome signaling ccaat/enhancer-binding protein beta mass-spectrometry-based proteomic approaches degrading anti-inflammatory sirtuin-1 immunosuppressive/anti-inflammatory cytokines directly proinflammatory il-1beta-rich microparticles nih-ncbi-geo datasets database high-fat diet feeding mapk-extracellular signal-regulated kinase pro-atherogenic stimuli-mediated induction affinity capture-mass spectrometry called cancer propagation article download pdf nih-ncbi-gene database [29] affinity capture-western blot graft-versus-host disease nih-geo dataset database intra-nuclear danger signals cleaves cytosolic pro-il-1β cytosolic multi-protein complexes epstein-barr virus latency developmental stage-specific mechanisms nih-geo datasets database caspase-1-mediated propagation omics-based molecular target golgi/er-independent manner [24] high-fat diet dormant pro-caspase-1 undergoes org/cgi-bin/carddisp mol cell proteomics caspase-1-sirtuin 1 pathway tumor necrosis factor-α convert inactive pro-caspase-1 nucleotide-binding oligomerization domain independent risk factor full access endothelial progenitor cells exocytotic secretory pathways resting human monocytes/macrophage nf-kb independent innate dna sensing van diepen ja activated caspase-1-based exosomes caspase-1/inflammasome pathway plays processing pro-il-1β metabolic disease research sensing danger signals signaling pathways related human gene database

Questions {❓}

• Caspase-1: is IL-1 just the tip of the ICEberg?
• Gov/cdd?

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         headline:Novel extracellular and nuclear caspase-1 and inflammasomes propagate inflammation and regulate gene expression: a comprehensive database mining study
         description: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. We conducted meticulous data analysis methods 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. 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. 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.
         datePublished:2016-11-14T00:00:00Z
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            Trafficking
            Nuclear gene regulation
            Inflammation propagation
            Exosome
            Oncology
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            Cancer Research
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      headline:Novel extracellular and nuclear caspase-1 and inflammasomes propagate inflammation and regulate gene expression: a comprehensive database mining study
      description: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. We conducted meticulous data analysis methods 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. 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. 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.
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      dateModified:2016-11-14T00:00:00Z
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         Caspase-1
         Trafficking
         Nuclear gene regulation
         Inflammation propagation
         Exosome
         Oncology
         Hematology
         Cancer Research
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            address:
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            address:
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            name:Lewis Katz School of Medicine at Temple University
            address:
               name:Centers for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, Philadelphia, USA
               type:PostalAddress
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            name:Lewis Katz School of Medicine at Temple University
            address:
               name:Department of Pharmacology, Lewis Katz School of Medicine at Temple University, Philadelphia, USA
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            address:
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               type:PostalAddress
            type:Organization
            name:Lewis Katz School of Medicine at Temple University
            address:
               name:Department of Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, USA
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      affiliation:
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            address:
               name:Centers for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, Philadelphia, USA
               type:PostalAddress
            type:Organization
            name:Lewis Katz School of Medicine at Temple University
            address:
               name:Department of Pharmacology, Lewis Katz School of Medicine at Temple University, Philadelphia, USA
               type:PostalAddress
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      affiliation:
            name:Lewis Katz School of Medicine at Temple University
            address:
               name:Centers for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, Philadelphia, USA
               type:PostalAddress
            type:Organization
            name:Lewis Katz School of Medicine at Temple University
            address:
               name:Cardiovascular Research and Thrombosis Research, Lewis Katz School of Medicine at Temple University, Philadelphia, USA
               type:PostalAddress
            type:Organization
            name:Lewis Katz School of Medicine at Temple University
            address:
               name:Department of Pharmacology, Lewis Katz School of Medicine at Temple University, Philadelphia, USA
               type:PostalAddress
            type:Organization
            name:Department of Physiology
            address:
               name:Department of Physiology, Philadelphia, USA
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Centers for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, Philadelphia, USA
      name:Department of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, China
      name:Centers for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, Philadelphia, USA
      name:Centers for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, Philadelphia, USA
      name:Centers for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, Philadelphia, USA
      name:Centers for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, Philadelphia, USA
      name:Centers for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, Philadelphia, USA
      name:Centers for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, Philadelphia, USA
      name:Centers for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, Philadelphia, USA
      name:Centers for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, Philadelphia, USA
      name:Centers for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, Philadelphia, USA
      name:Centers for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, Philadelphia, USA
      name:Department of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, China
      name:Department of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, China
      name:Centers for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, Philadelphia, USA
      name:Centers for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, Philadelphia, USA
      name:Centers for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, Philadelphia, USA
      name:Department of Pharmacology, Lewis Katz School of Medicine at Temple University, Philadelphia, USA
      name:Centers for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, Philadelphia, USA
      name:Department of Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, USA
      name:Centers for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, Philadelphia, USA
      name:Department of Pharmacology, Lewis Katz School of Medicine at Temple University, Philadelphia, USA
      name:Centers for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, Philadelphia, USA
      name:Cardiovascular Research and Thrombosis Research, Lewis Katz School of Medicine at Temple University, Philadelphia, USA
      name:Department of Pharmacology, Lewis Katz School of Medicine at Temple University, Philadelphia, USA
      name:Department of Physiology, Philadelphia, USA

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