Semi-Quantitative Mass Spectrometry in AML Cells Identifies New Non-Genomic Targets of the EZH2 Methyltransferase
AbstractAlterations to the gene encoding the EZH2 (KMT6A) methyltransferase, including both gain-of-function and loss-of-function, have been linked to a variety of haematological malignancies and solid tumours, suggesting a complex, context-dependent role of this methyltransferase. The successful implementation of molecularly targeted therapies against EZH2 requires a greater understanding of the potential mechanisms by which EZH2 contributes to cancer. One aspect of this effort is the mapping of EZH2 partner proteins and cellular targets. To this end we performed affinity-purification mass spectrometry in the FAB-M2 HL-60 acute myeloid leukaemia (AML) cell line before and after all-trans retinoic acid-induced differentiation. These studies identified new EZH2 interaction partners and potential non-histone substrates for EZH2-mediated methylation. Our results suggest that EZH2 is involved in the regulation of translation through interactions with a number of RNA binding proteins and by methylating key components of protein synthesis such as eEF1A1. Given that deregulated mRNA translation is a frequent feature of cancer and that eEF1A1 is highly expressed in many human tumours, these findings present new possibilities for the therapeutic targeting of EZH2 in AML. View Full-Text
- Supplementary File 1:
Supplementary (ZIP, 7176 KB)
Share & Cite This Article
Sbirkov, Y.; Kwok, C.; Bhamra, A.; Thompson, A.J.; Gil, V.; Zelent, A.; Petrie, K. Semi-Quantitative Mass Spectrometry in AML Cells Identifies New Non-Genomic Targets of the EZH2 Methyltransferase. Int. J. Mol. Sci. 2017, 18, 1440.
Sbirkov Y, Kwok C, Bhamra A, Thompson AJ, Gil V, Zelent A, Petrie K. Semi-Quantitative Mass Spectrometry in AML Cells Identifies New Non-Genomic Targets of the EZH2 Methyltransferase. International Journal of Molecular Sciences. 2017; 18(7):1440.Chicago/Turabian Style
Sbirkov, Yordan; Kwok, Colin; Bhamra, Amandeep; Thompson, Andrew J.; Gil, Veronica; Zelent, Arthur; Petrie, Kevin. 2017. "Semi-Quantitative Mass Spectrometry in AML Cells Identifies New Non-Genomic Targets of the EZH2 Methyltransferase." Int. J. Mol. Sci. 18, no. 7: 1440.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.