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Burkitt’s lymphoma-associated c-Myc mutations converge on a dramatically altered target gene response and implicate Nol5a/Nop56 in oncogenesis

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...

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Autores principales: Cowling, Victoria H., Turner, Scott A., Cole, Michael D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5003617/
https://www.ncbi.nlm.nih.gov/pubmed/24013231
http://dx.doi.org/10.1038/onc.2013.338
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author Cowling, Victoria H.
Turner, Scott A.
Cole, Michael D.
author_facet Cowling, Victoria H.
Turner, Scott A.
Cole, Michael D.
author_sort Cowling, Victoria H.
collection PubMed
description 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 rRNA 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.
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spelling pubmed-50036172016-08-29 Burkitt’s lymphoma-associated c-Myc mutations converge on a dramatically altered target gene response and implicate Nol5a/Nop56 in oncogenesis Cowling, Victoria H. Turner, Scott A. Cole, Michael D. Oncogene Article 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 rRNA 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. 2013-09-09 2014-07-03 /pmc/articles/PMC5003617/ /pubmed/24013231 http://dx.doi.org/10.1038/onc.2013.338 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Cowling, Victoria H.
Turner, Scott A.
Cole, Michael D.
Burkitt’s lymphoma-associated c-Myc mutations converge on a dramatically altered target gene response and implicate Nol5a/Nop56 in oncogenesis
title Burkitt’s lymphoma-associated c-Myc mutations converge on a dramatically altered target gene response and implicate Nol5a/Nop56 in oncogenesis
title_full Burkitt’s lymphoma-associated c-Myc mutations converge on a dramatically altered target gene response and implicate Nol5a/Nop56 in oncogenesis
title_fullStr Burkitt’s lymphoma-associated c-Myc mutations converge on a dramatically altered target gene response and implicate Nol5a/Nop56 in oncogenesis
title_full_unstemmed Burkitt’s lymphoma-associated c-Myc mutations converge on a dramatically altered target gene response and implicate Nol5a/Nop56 in oncogenesis
title_short Burkitt’s lymphoma-associated c-Myc mutations converge on a dramatically altered target gene response and implicate Nol5a/Nop56 in oncogenesis
title_sort burkitt’s lymphoma-associated c-myc mutations converge on a dramatically altered target gene response and implicate nol5a/nop56 in oncogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5003617/
https://www.ncbi.nlm.nih.gov/pubmed/24013231
http://dx.doi.org/10.1038/onc.2013.338
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