| http://purl.uniprot.org/citations/24633224 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24633224 | http://www.w3.org/2000/01/rdf-schema#comment | "Lysosomal membrane permeabilization is an essential step in TRAIL-induced apoptosis of liver cancer cell lines. TRAIL-induced lysosomal membrane permeabilization is mediated by the multifunctional sorting protein PACS-2 and repressed by the E3 ligases cIAP-1 and cIAP-2. Despite the opposing roles for PACS-2 and cIAPs in TRAIL-induced apoptosis, an interaction between these proteins has yet to be examined. Herein, we report that cIAP-1 and cIAP-2 confer TRAIL resistance to hepatobiliary cancer cell lines by reducing PACS-2 levels. Under basal conditions, PACS-2 underwent K48-linked poly-ubiquitination, resulting in PACS-2 proteasomal degradation. Biochemical assays showed cIAP-1 and cIAP-2 interacted with PACS-2 in vitro and co-immunoprecipitation studies demonstrated that the two cIAPs bound PACS-2 in vivo. More importantly, both cIAP-1 and cIAP-2 directly mediated PACS-2 ubiquitination in a cell-free assay. Single c-Iap-1 or c-Iap-2 gene knock-outs in mouse hepatocytes did not lead to PACS-2 accumulation. However, deletion of both cIAP-1 and cIAP-2 reduced PACS-2 ubiquitination, which increased PACS-2 levels and sensitized HuH-7 cells to TRAIL-induced lysosomal membrane permeabilization and apoptosis. Correspondingly, deletion of cIAPs sensitized wild-type, but not PACS-2-deficient hepatocarcinoma cells or Pacs-2-/-mouse hepatocytes to TRAIL-induced apoptosis. Together, these data suggest cIAPs constitutively downregulate PACS-2 by polyubiquitination and proteasomal degradation, thereby restraining TRAIL-induced killing of liver cancer cells."xsd:string |
| http://purl.uniprot.org/citations/24633224 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pone.0092124"xsd:string |
| http://purl.uniprot.org/citations/24633224 | http://purl.uniprot.org/core/author | "Franke A."xsd:string |
| http://purl.uniprot.org/citations/24633224 | http://purl.uniprot.org/core/author | "Thomas G."xsd:string |
| http://purl.uniprot.org/citations/24633224 | http://purl.uniprot.org/core/author | "Yagita H."xsd:string |
| http://purl.uniprot.org/citations/24633224 | http://purl.uniprot.org/core/author | "Gores G.J."xsd:string |
| http://purl.uniprot.org/citations/24633224 | http://purl.uniprot.org/core/author | "Bronk S.F."xsd:string |
| http://purl.uniprot.org/citations/24633224 | http://purl.uniprot.org/core/author | "Guicciardi M.E."xsd:string |
| http://purl.uniprot.org/citations/24633224 | http://purl.uniprot.org/core/author | "Werneburg N.W."xsd:string |
| http://purl.uniprot.org/citations/24633224 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/24633224 | http://purl.uniprot.org/core/name | "PLoS One"xsd:string |
| http://purl.uniprot.org/citations/24633224 | http://purl.uniprot.org/core/pages | "e92124"xsd:string |
| http://purl.uniprot.org/citations/24633224 | http://purl.uniprot.org/core/title | "Cellular inhibitor of apoptosis (cIAP)-mediated ubiquitination of phosphofurin acidic cluster sorting protein 2 (PACS-2) negatively regulates tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) cytotoxicity."xsd:string |
| http://purl.uniprot.org/citations/24633224 | http://purl.uniprot.org/core/volume | "9"xsd:string |
| http://purl.uniprot.org/citations/24633224 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/24633224 |
| http://purl.uniprot.org/citations/24633224 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/24633224 |
| http://purl.uniprot.org/uniprot/#_A0A0U5EM55-mappedCitation-24633224 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24633224 |
| http://purl.uniprot.org/uniprot/#_E0CZ20-mappedCitation-24633224 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24633224 |
| http://purl.uniprot.org/uniprot/#_E0CZ68-mappedCitation-24633224 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24633224 |
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| http://purl.uniprot.org/uniprot/#_A2CGA5-mappedCitation-24633224 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24633224 |
| http://purl.uniprot.org/uniprot/#_B2R8N8-mappedCitation-24633224 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24633224 |
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| http://purl.uniprot.org/uniprot/#_P39429-mappedCitation-24633224 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24633224 |