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Abstract
c-Myc is a potent driver of many human cancers. Since strategies for directly targeting c-Myc protein have had limited success, upstream regulators and downstream effectors of c-Myc are being investigated as alternatives for therapeutic intervention. c-Myc regulates transcription and formation of the mRNA cap, which is important for transcript maturation and translation. However, the direct mechanism by which c-Myc upregulates mRNA capping is unclear. mRNA cap formation initiates with the linkage of inverted guanosine via a triphosphate bridge to the first transcribed nucleotide, catalysed by mRNA capping enzyme (CE/RNGTT). Here we report that c-Myc increases the recruitment of catalytically active CE to RNA polymerase II and to its target genes. c-Myc-induced target gene expression, cell proliferation and cell transformation is highly dependent on CE, but only when c-Myc is deregulated. Cells retaining normal control of c-Myc expression are insensitive to repression of CE. c-Myc expression is also dependent on CE. Therefore, inhibiting CE provides an attractive route for selective therapeutic targeting of cancer cells which have acquired deregulated c-Myc.
Original language | English |
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Pages (from-to) | 82273-82288 |
Number of pages | 16 |
Journal | Oncotarget |
Volume | 7 |
Issue number | 50 |
Early online date | 16 Oct 2016 |
DOIs | |
Publication status | Published - 16 Oct 2016 |
Keywords
- c-Myc
- mRNA cap
- transcription
- translation
- cell proliferation
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Projects
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Student Theses
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Investigating the role of mRNA capping enzyme in C-MYC function
Author: Lombardi, O., 2017Supervisor: Cowling, V. (Supervisor)
Student thesis: Doctoral Thesis › Doctor of Philosophy
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