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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 language | English |
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Pages (from-to) | 3519–3527 |
Number of pages | 9 |
Journal | Oncogene |
Volume | 33 |
Early online date | 9 Sept 2013 |
DOIs | |
Publication status | Published - 3 Jul 2014 |
Keywords
- Myc
- lymphoma
- mutations
- Burkitt's
- transcription
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