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

V. H. Cowling, S. A. Turner, M. D. Cole (Lead / Corresponding author)

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    39 Citations (Scopus)

    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.Oncogene advance online publication, 9 September 2013; doi:10.1038/onc.2013.338.
    Original languageEnglish
    Pages (from-to)3519–3527
    Number of pages9
    JournalOncogene
    Volume33
    Early online date9 Sept 2013
    DOIs
    Publication statusPublished - 3 Jul 2014

    Keywords

    • Myc
    • lymphoma
    • mutations
    • Burkitt's
    • transcription

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