| http://purl.uniprot.org/citations/22266862 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22266862 | http://www.w3.org/2000/01/rdf-schema#comment | "Glioblastoma is the most common primary brain tumor with a very poor prognosis, calling for novel treatment strategies. Here, we provide first evidence that histone deacetylase inhibitors (HDACI) prime glioblastoma cells for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) -induced apoptosis at least in part by c-myc-mediated downregulation of cellular FLICE-inhibitory protein (cFLIP). Pretreatment with distinct HDACI (MS275, suberoylanilide hydroxamic acid, valproic acid) significantly enhances TRAIL-induced apoptosis in several glioblastoma cell lines. Monitoring a panel of apoptosis-regulatory proteins revealed that MS275 reduces the expression of cFLIP(L) and cFLIP(S). This leads to decreased recruitment of cFLIP(L) and cFLIP(S) and increased activation of caspase-8 to the TRAIL death-inducing signaling complex, resulting in enhanced cleavage of caspase-8, -9 and -3 and caspase-dependent apoptosis. Also, MS275 promotes TRAIL-triggered processing of Bid, activation of Bax, loss of mitochondrial membrane potential and release of cytochrome c. MS275-mediated downregulation of cFLIP occurs at the mRNA level independent of proteasome- or caspase-mediated degradation, and is preceded by upregulation of nuclear levels of c-myc, a transcriptional repressor of cFLIP. Notably, MS275 causes increased binding of c-myc to the cFLIP promoter and reduces cFLIP promoter activity. Indeed, knockdown of c-myc partially rescues cFLIP(L) from MS275-inferred downregulation and significantly decreases TRAIL- and MS275-induced apoptosis. Also, overexpression of cFLIP(L) or cFLIP(S) significantly reduces MS275- and TRAIL-induced apoptosis. Importantly, MS275 sensitizes primary cultured glioblastoma cells towards TRAIL and cooperates with TRAIL to reduce long-term clonogenic survival of glioblastoma cells and to suppress glioblastoma growth in vivo underscoring the clinical relevance of this approach. Thus, these findings demonstrate that HDACI represent a promising strategy to prime glioblastoma for TRAIL-induced apoptosis by targeting cFLIP."xsd:string |
| http://purl.uniprot.org/citations/22266862 | http://purl.org/dc/terms/identifier | "doi:10.1038/onc.2011.614"xsd:string |
| http://purl.uniprot.org/citations/22266862 | http://purl.uniprot.org/core/author | "Fulda S."xsd:string |
| http://purl.uniprot.org/citations/22266862 | http://purl.uniprot.org/core/author | "Hacker S."xsd:string |
| http://purl.uniprot.org/citations/22266862 | http://purl.uniprot.org/core/author | "Lausen J."xsd:string |
| http://purl.uniprot.org/citations/22266862 | http://purl.uniprot.org/core/author | "Debatin K.M."xsd:string |
| http://purl.uniprot.org/citations/22266862 | http://purl.uniprot.org/core/author | "Bangert A."xsd:string |
| http://purl.uniprot.org/citations/22266862 | http://purl.uniprot.org/core/author | "Abhari B.A."xsd:string |
| http://purl.uniprot.org/citations/22266862 | http://purl.uniprot.org/core/author | "Cristofanon S."xsd:string |
| http://purl.uniprot.org/citations/22266862 | http://purl.uniprot.org/core/author | "Kolodziej S."xsd:string |
| http://purl.uniprot.org/citations/22266862 | http://purl.uniprot.org/core/author | "Vellanki S.H."xsd:string |
| http://purl.uniprot.org/citations/22266862 | http://purl.uniprot.org/core/author | "Eckhardt I."xsd:string |
| http://purl.uniprot.org/citations/22266862 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/22266862 | http://purl.uniprot.org/core/name | "Oncogene"xsd:string |
| http://purl.uniprot.org/citations/22266862 | http://purl.uniprot.org/core/pages | "4677-4688"xsd:string |
| http://purl.uniprot.org/citations/22266862 | http://purl.uniprot.org/core/title | "Histone deacetylase inhibitors sensitize glioblastoma cells to TRAIL-induced apoptosis by c-myc-mediated downregulation of cFLIP."xsd:string |
| http://purl.uniprot.org/citations/22266862 | http://purl.uniprot.org/core/volume | "31"xsd:string |
| http://purl.uniprot.org/citations/22266862 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/22266862 |
| http://purl.uniprot.org/citations/22266862 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/22266862 |
| http://purl.uniprot.org/uniprot/P50591#attribution-ABE379C7ECF2AFE579BCC28C9AD9C7C7 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/22266862 |
| http://purl.uniprot.org/uniprot/#_O14763-mappedCitation-22266862 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22266862 |
| http://purl.uniprot.org/uniprot/#_Q13158-mappedCitation-22266862 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22266862 |
| http://purl.uniprot.org/uniprot/#_Q14790-mappedCitation-22266862 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22266862 |
| http://purl.uniprot.org/uniprot/#_P50591-mappedCitation-22266862 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22266862 |