| http://purl.uniprot.org/citations/27612013 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/27612013 | http://www.w3.org/2000/01/rdf-schema#comment | "Recombinant TRAIL and agonistic antibodies to death receptors (DRs) have been in clinical trial but displayed limited anti-cancer efficacy. Lack of functional DR expression in tumors is a major limiting factor. We report here that chromatin regulator KDM4A/JMJD2A, not KDM4B, has a pivotal role in silencing tumor cell expression of both TRAIL and its receptor DR5. In TRAIL-sensitive and -resistant cancer cells of lung, breast and prostate, KDM4A small-molecule inhibitor compound-4 (C-4) or gene silencing strongly induces TRAIL and DR5 expression, and causes TRAIL-dependent apoptotic cell death. KDM4A inhibition also strongly sensitizes cells to TRAIL. C-4 alone potently inhibits tumor growth with marked induction of TRAIL and DR5 expression in the treated tumors and effectively sensitizes them to the newly developed TRAIL-inducer ONC201. Mechanistically, C-4 does not appear to act through the Akt-ERK-FOXO3a pathway. Instead, it switches histone modifying enzyme complexes at promoters of TRAIL and DR5 transcriptional activator CHOP gene by dissociating KDM4A and nuclear receptor corepressor (NCoR)-HDAC complex and inducing the recruitment of histone acetylase CBP. Thus, our results reveal KDM4A as a key epigenetic silencer of TRAIL and DR5 in tumors and establish inhibitors of KDM4A as a novel strategy for effectively sensitizing tumors to TRAIL pathway-based therapeutics."xsd:string |
| http://purl.uniprot.org/citations/27612013 | http://purl.org/dc/terms/identifier | "doi:10.1038/cdd.2016.92"xsd:string |
| http://purl.uniprot.org/citations/27612013 | http://purl.uniprot.org/core/author | "Chen X."xsd:string |
| http://purl.uniprot.org/citations/27612013 | http://purl.uniprot.org/core/author | "Chen P."xsd:string |
| http://purl.uniprot.org/citations/27612013 | http://purl.uniprot.org/core/author | "Zhang Y."xsd:string |
| http://purl.uniprot.org/citations/27612013 | http://purl.uniprot.org/core/author | "Wang J."xsd:string |
| http://purl.uniprot.org/citations/27612013 | http://purl.uniprot.org/core/author | "Xu J."xsd:string |
| http://purl.uniprot.org/citations/27612013 | http://purl.uniprot.org/core/author | "Wang H."xsd:string |
| http://purl.uniprot.org/citations/27612013 | http://purl.uniprot.org/core/author | "Wang L.Y."xsd:string |
| http://purl.uniprot.org/citations/27612013 | http://purl.uniprot.org/core/author | "Duan Z."xsd:string |
| http://purl.uniprot.org/citations/27612013 | http://purl.uniprot.org/core/author | "Chen H.W."xsd:string |
| http://purl.uniprot.org/citations/27612013 | http://purl.uniprot.org/core/author | "Kung H.J."xsd:string |
| http://purl.uniprot.org/citations/27612013 | http://purl.uniprot.org/core/author | "Cai D."xsd:string |
| http://purl.uniprot.org/citations/27612013 | http://purl.uniprot.org/core/author | "Zou J.X."xsd:string |
| http://purl.uniprot.org/citations/27612013 | http://purl.uniprot.org/core/date | "2016"xsd:gYear |
| http://purl.uniprot.org/citations/27612013 | http://purl.uniprot.org/core/name | "Cell Death Differ"xsd:string |
| http://purl.uniprot.org/citations/27612013 | http://purl.uniprot.org/core/pages | "1886-1896"xsd:string |
| http://purl.uniprot.org/citations/27612013 | http://purl.uniprot.org/core/title | "Silencing the epigenetic silencer KDM4A for TRAIL and DR5 simultaneous induction and antitumor therapy."xsd:string |
| http://purl.uniprot.org/citations/27612013 | http://purl.uniprot.org/core/volume | "23"xsd:string |
| http://purl.uniprot.org/citations/27612013 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/27612013 |
| http://purl.uniprot.org/citations/27612013 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/27612013 |
| http://purl.uniprot.org/uniprot/#_A0A0U5EM55-mappedCitation-27612013 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27612013 |
| http://purl.uniprot.org/uniprot/#_B7Z3M7-mappedCitation-27612013 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27612013 |
| http://purl.uniprot.org/uniprot/#_B4DGH3-mappedCitation-27612013 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27612013 |