COP9 Signalosome Controls the Degradation of Cytosolic Misfolded Proteins and Protects Against Cardiac Proteotoxicity
Su H, Li J, Zhang H, Ma W, Wei N, Liu J, Wang X. COP9 Signalosome Controls the Degradation of Cytosolic Misfolded Proteins and Protects Against Cardiac Proteotoxicity. Circulation Research 2015, 117: 956-966. PMID: 26383969, PMCID: PMC4636927, DOI: 10.1161/circresaha.115.306783.Peer-Reviewed Original ResearchMeSH KeywordsAlpha-Crystallin B ChainAnimalsAnimals, NewbornAutophagyCarrier ProteinsCells, CulturedCOP9 Signalosome ComplexCullin ProteinsCytosolFemaleGenotypeHeart DiseasesHeart VentriclesMaleMice, Inbred C57BLMice, KnockoutMicrotubule-Associated ProteinsMyocytes, CardiacPhenotypeProtein FoldingProteolysisRats, Sprague-DawleyRNA InterferenceSignal TransductionTime FactorsTransfectionUbiquitinationConceptsCullin-RING ligasesCSN8/CSNCOP9 signalosomeMisfolded proteinsProtein aggregatesCardiac proteotoxicitySurrogate misfolded proteinUbiquitin-proteasome systemDeneddylation activityCSN subunitsUbiquitin ligasesG missense mutationTotal ubiquitinated proteinsUbiquitinated proteinsCardiac proteinopathyProtein degradationLigasesUbiquitinationMissense mutationsProteinLC3-IIProteotoxicityReduced levelsCultured cardiomyocytesHypomorphismPriming the proteasome by protein kinase G: a novel cardioprotective mechanism of sildenafil
Zhang H, Wang X. Priming the proteasome by protein kinase G: a novel cardioprotective mechanism of sildenafil. Future Cardiology 2015, 11: 177-189. PMID: 25760877, PMCID: PMC4370174, DOI: 10.2217/fca.15.3.Peer-Reviewed Original ResearchConceptsProtein kinase GProtein quality controlMost cellular proteinsKinase GNovel cardioprotective mechanismProteasome enhancementCardiac protein quality controlProtein kinase G activationMisfolded proteinsProtein hemostasisCellular proteinsProteasomal degradationCardiac proteinopathyHuman failing heartsProteinProteasomeNew therapeutic strategiesG activationTherapeutic strategiesMajor pathogenic factorFunctional insufficiencyCardioprotective mechanismsLarge subsetDegradationMechanism