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All rights reserved. http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Large Corpus Document http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RA9bNcRXrXxHrxVp0WxID0f2V22s4HeTbynGSvk2fvhQw#_6 http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/version 1.4 http://www.tkuhn.ch/bel2nanopub/RA9bNcRXrXxHrxVp0WxID0f2V22s4HeTbynGSvk2fvhQw#_5 http://www.w3.org/ns/prov#value Oncogene activation increases susceptibility to apoptosis. Thus, tumorigenesis must depend, in part, on compensating mutations that protect from programmed cell death. A functional screen for cDNAs that could counteract the proapoptotic effects of the myc oncogene identified two related bHLH family members, Twist and Dermo1. Both of these proteins inhibited oncogene- and p53-dependent cell death. Twist expression bypassed p53-induced growth arrest. These effects correlated with an ability of Twist to interfere with activation of a p53-dependent reporter and to impair induction of p53 target genes in response to DNA damage. An underlying explanation for this observation may be provided by the ability of Twist to reduce expression of the ARF tumor suppressor. Thus, Twist may affect p53 indirectly through modulation of the ARF/MDM2/p53 pathway. Consistent with a role as a potential oncoprotein, Twist expression promoted colony formation of E1A/ras-transformed mouse embryo fibroblasts (MEFs) in soft agar. Furthermore, Twist was inappropriately expressed in 50% of rhabdomyosarcomas, a tumor that arises from skeletal muscle precursors that fail to differentiate. Twist is known to block myogenic differentiation. Thus, Twist may play multiple roles in the formation of rhabdomyosarcomas, halting terminal differentiation, inhibiting apoptosis, and interfering with the p53 tumor-suppressor pathway. http://www.tkuhn.ch/bel2nanopub/RA9bNcRXrXxHrxVp0WxID0f2V22s4HeTbynGSvk2fvhQw#_5 http://www.w3.org/ns/prov#wasQuotedFrom http://www.ncbi.nlm.nih.gov/pubmed/10485844 http://www.tkuhn.ch/bel2nanopub/RA9bNcRXrXxHrxVp0WxID0f2V22s4HeTbynGSvk2fvhQw#_6 http://www.w3.org/2000/01/rdf-schema#label Selventa http://www.tkuhn.ch/bel2nanopub/RA9bNcRXrXxHrxVp0WxID0f2V22s4HeTbynGSvk2fvhQw#assertion http://www.w3.org/ns/prov#hadPrimarySource http://www.ncbi.nlm.nih.gov/pubmed/10485844 http://www.tkuhn.ch/bel2nanopub/RA9bNcRXrXxHrxVp0WxID0f2V22s4HeTbynGSvk2fvhQw#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://www.tkuhn.ch/bel2nanopub/RA9bNcRXrXxHrxVp0WxID0f2V22s4HeTbynGSvk2fvhQw#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://www.tkuhn.ch/bel2nanopub/RA9bNcRXrXxHrxVp0WxID0f2V22s4HeTbynGSvk2fvhQw#_5 http://www.tkuhn.ch/bel2nanopub/RA9bNcRXrXxHrxVp0WxID0f2V22s4HeTbynGSvk2fvhQw#pubinfo http://www.tkuhn.ch/bel2nanopub/RA9bNcRXrXxHrxVp0WxID0f2V22s4HeTbynGSvk2fvhQw http://purl.org/dc/terms/created 2014-07-03T14:29:48.382+02:00 http://www.tkuhn.ch/bel2nanopub/RA9bNcRXrXxHrxVp0WxID0f2V22s4HeTbynGSvk2fvhQw http://purl.org/pav/createdBy http://orcid.org/0000-0001-6818-334X http://www.tkuhn.ch/bel2nanopub/RA9bNcRXrXxHrxVp0WxID0f2V22s4HeTbynGSvk2fvhQw http://purl.org/pav/createdBy http://orcid.org/0000-0002-1267-0234