| http://purl.uniprot.org/citations/32723872 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/32723872 | http://www.w3.org/2000/01/rdf-schema#comment | "α1-Antitrypsin (AAT) encoded by the SERPINA1 gene is an acute-phase protein synthesized in the liver and secreted into the circulation. Its primary role is to protect lung tissue by inhibiting neutrophil elastase. The Z allele of SERPINA1 encodes a mutant AAT, named ATZ, that changes the protein structure and leads to its misfolding and polymerization, which cause endoplasmic reticulum (ER) stress and liver disease through a gain-of-function toxic mechanism. Hepatic retention of ATZ results in deficiency of one of the most important circulating proteinase inhibitors and predisposes to early-onset emphysema through a loss-of-function mechanism. The pathogenetic mechanisms underlying the liver disease are not completely understood. C/EBP-homologous protein (CHOP), a transcription factor induced by ER stress, was found among the most up-regulated genes in livers of PiZ mice that express ATZ and in human livers of patients homozygous for the Z allele. Compared with controls, juvenile PiZ/Chop-/- mice showed reduced hepatic ATZ and a transcriptional response indicative of decreased ER stress by RNA-Seq analysis. Livers of PiZ/Chop-/- mice also showed reduced SERPINA1 mRNA levels. By chromatin immunoprecipitations and luciferase reporter-based transfection assays, CHOP was found to up-regulate SERPINA1 cooperating with c-JUN, which was previously shown to up-regulate SERPINA1, thus aggravating hepatic accumulation of ATZ. Increased CHOP levels were detected in diseased livers of children homozygous for the Z allele. In summary, CHOP and c-JUN up-regulate SERPINA1 transcription and play an important role in hepatic disease by increasing the burden of proteotoxic ATZ, particularly in the pediatric population."xsd:string |
| http://purl.uniprot.org/citations/32723872 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.ra120.014307"xsd:string |
| http://purl.uniprot.org/citations/32723872 | http://purl.uniprot.org/core/author | "Mueller C."xsd:string |
| http://purl.uniprot.org/citations/32723872 | http://purl.uniprot.org/core/author | "Brunetti-Pierri N."xsd:string |
| http://purl.uniprot.org/citations/32723872 | http://purl.uniprot.org/core/author | "De Cegli R."xsd:string |
| http://purl.uniprot.org/citations/32723872 | http://purl.uniprot.org/core/author | "Nusco E."xsd:string |
| http://purl.uniprot.org/citations/32723872 | http://purl.uniprot.org/core/author | "Piccolo P."xsd:string |
| http://purl.uniprot.org/citations/32723872 | http://purl.uniprot.org/core/author | "Ferriero R."xsd:string |
| http://purl.uniprot.org/citations/32723872 | http://purl.uniprot.org/core/author | "Teckman J."xsd:string |
| http://purl.uniprot.org/citations/32723872 | http://purl.uniprot.org/core/author | "Campione S."xsd:string |
| http://purl.uniprot.org/citations/32723872 | http://purl.uniprot.org/core/author | "Carissimo A."xsd:string |
| http://purl.uniprot.org/citations/32723872 | http://purl.uniprot.org/core/author | "Attanasio S."xsd:string |
| http://purl.uniprot.org/citations/32723872 | http://purl.uniprot.org/core/author | "Gernoux G."xsd:string |
| http://purl.uniprot.org/citations/32723872 | http://purl.uniprot.org/core/date | "2020"xsd:gYear |
| http://purl.uniprot.org/citations/32723872 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/32723872 | http://purl.uniprot.org/core/pages | "13213-13223"xsd:string |
| http://purl.uniprot.org/citations/32723872 | http://purl.uniprot.org/core/title | "CHOP and c-JUN up-regulate the mutant Z alphapisub>1pi/sub>-antitrypsin, exacerbating its aggregation and liver proteotoxicity."xsd:string |
| http://purl.uniprot.org/citations/32723872 | http://purl.uniprot.org/core/volume | "295"xsd:string |
| http://purl.uniprot.org/citations/32723872 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/32723872 |
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| http://purl.uniprot.org/uniprot/#_A0A384MDQ7-mappedCitation-32723872 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32723872 |