| http://purl.uniprot.org/citations/10541554 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/10541554 | http://www.w3.org/2000/01/rdf-schema#comment | "The bmi-1 and myc oncogenes collaborate strongly in murine lymphomagenesis, but the basis for this collaboration was not understood. We recently identified the ink4a-ARF tumor suppressor locus as a critical downstream target of the Polycomb-group transcriptional repressor Bmi-1. Others have shown that part of Myc's ability to induce apoptosis depends on induction of p19arf. Here we demonstrate that down-regulation of ink4a-ARF by Bmi-1 underlies its ability to cooperate with Myc in tumorigenesis. Heterozygosity for bmi-1 inhibits lymphomagenesis in Emu-myc mice by enhancing c-Myc-induced apoptosis. We observe increased apoptosis in bmi-1(-/-) lymphoid organs, which can be rescued by deletion of ink4a-ARF or overexpression of bcl2. Furthermore, Bmi-1 collaborates with Myc in enhancing proliferation and transformation of primary embryo fibroblasts (MEFs) in an ink4a-ARF dependent manner, by prohibiting Myc-mediated induction of p19arf and apoptosis. We observe strong collaboration between the Emu-myc transgene and heterozygosity for ink4a-ARF, which is accompanied by loss of the wild-type ink4a-ARF allele and formation of highly aggressive B-cell lymphomas. Together, these results reinforce the critical role of Bmi-1 as a dose-dependent regulator of ink4a-ARF, which on its turn acts to prevent tumorigenesis on activation of oncogenes such as c-myc."xsd:string |
| http://purl.uniprot.org/citations/10541554 | http://purl.org/dc/terms/identifier | "doi:10.1101/gad.13.20.2678"xsd:string |
| http://purl.uniprot.org/citations/10541554 | http://purl.uniprot.org/core/author | "Jacobs J.J."xsd:string |
| http://purl.uniprot.org/citations/10541554 | http://purl.uniprot.org/core/author | "Berns A."xsd:string |
| http://purl.uniprot.org/citations/10541554 | http://purl.uniprot.org/core/author | "Scheijen B."xsd:string |
| http://purl.uniprot.org/citations/10541554 | http://purl.uniprot.org/core/author | "van Lohuizen M."xsd:string |
| http://purl.uniprot.org/citations/10541554 | http://purl.uniprot.org/core/author | "Voncken J.W."xsd:string |
| http://purl.uniprot.org/citations/10541554 | http://purl.uniprot.org/core/author | "Kieboom K."xsd:string |
| http://purl.uniprot.org/citations/10541554 | http://purl.uniprot.org/core/date | "1999"xsd:gYear |
| http://purl.uniprot.org/citations/10541554 | http://purl.uniprot.org/core/name | "Genes Dev"xsd:string |
| http://purl.uniprot.org/citations/10541554 | http://purl.uniprot.org/core/pages | "2678-2690"xsd:string |
| http://purl.uniprot.org/citations/10541554 | http://purl.uniprot.org/core/title | "Bmi-1 collaborates with c-Myc in tumorigenesis by inhibiting c-Myc-induced apoptosis via INK4a/ARF."xsd:string |
| http://purl.uniprot.org/citations/10541554 | http://purl.uniprot.org/core/volume | "13"xsd:string |
| http://purl.uniprot.org/citations/10541554 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/10541554 |
| http://purl.uniprot.org/citations/10541554 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/10541554 |
| http://purl.uniprot.org/uniprot/#_E0CZD1-mappedCitation-10541554 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10541554 |
| http://purl.uniprot.org/uniprot/#_A0A991B922-mappedCitation-10541554 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10541554 |
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| http://purl.uniprot.org/uniprot/#_A2ASR7-mappedCitation-10541554 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/10541554 |
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