title: Burkitt's lymphoma-associated c-Myc mutations converge on a dramatically altered target gene response and implicate Nol5a/Nop56 in oncogenesis.
abstract: Burkitt's lymphomas (BLs) acquire consistent point mutations in a conserved domain of Myc, Myc Box I. We report that the enhanced transforming activity of BL-associated Myc mutants can be uncoupled from loss of phosphorylation and increased protein stability. Furthermore, two different BL-associated Myc mutations induced similar gene expression profiles independently of T58 phosphorylation, and these profiles are dramatically different from MycWT. Nol5a/Nop56, which is required for ribosomal RNA methylation, was identified as a gene hyperactivated by the BL-associated Myc mutants. We show that Nol5a is necessary for Myc-induced cell transformation, enhances MycWT-induced cell transformation and increases the size of MycWT-induced tumors. Thus, Nol5a expands the link between Myc-induced regulation of nucleolar target genes, which are rate limiting for cell transformation and tumor growth.
authors.affiliation: Department of Pharmacology, Geisel School of Medicine at Dartmouth, Norris Cotton Cancer Center, One Medical Center Drive, Lebanon, NH, USA.
authors.forename: V H
authors.initials: VH
authors.lastname: Cowling
authors.affiliation: Department of Genetics, Geisel School of Medicine at Dartmouth, Norris Cotton Cancer Center, One Medical Center Drive, Lebanon, NH, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Turner
authors.affiliation: 1] Department of Pharmacology, Geisel School of Medicine at Dartmouth, Norris Cotton Cancer Center, One Medical Center Drive, Lebanon, NH, USA [2] Department of Genetics, Geisel School of Medicine at Dartmouth, Norris Cotton Cancer Center, One Medical Center Drive, Lebanon, NH, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Cole
mesh_terms: D000818:Animals; D002051:Burkitt Lymphoma / Q000235:genetics* / Q000473:pathology*; D063646:Carcinogenesis / Q000235:genetics*; D002460:Cell Line; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D005260:Female; D020869:Gene Expression Profiling; D006657:Histones / Q000235:genetics; D006801:Humans; D051379:Mice; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D012270:Ribosomes / Q000235:genetics
chemical_list: D006657:Histones; C000591280:NOP56 protein, rat; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc