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Comment
. 2018 Aug 1;37(15):e99978.
doi: 10.15252/embj.201899978. Epub 2018 Jul 2.

A wobbly road to drug resistance in melanoma: tRNA-modifying enzymes in translation reprogramming

Mary McMahon  1 , Davide Ruggero  1   2
Affiliations
Free PMC article
Comment

A wobbly road to drug resistance in melanoma: tRNA-modifying enzymes in translation reprogramming

Mary McMahon et al. EMBO J. .
Free PMC article

Abstract

Alterations in transcript‐specific translation are emerging as a driver of cellular transformation and cancer etiology. A new study provides evidence for enhanced codon‐dependent translation of hypoxia‐inducible factor 1α in promoting glycolytic metabolism and drug resistance in melanoma cells. This specialized translation reprogramming relies, in part, on mTORC2‐mediated phosphorylation of enzymes modifying the wobble position of the transfer RNA anticodon.

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Figures

Figure 1
Figure 1. Codon‐dependent translation regulation of HIF1α couples glycolytic metabolism to drug resistance in melanoma
Cartoon depicts the proposed mechanism by which increased activation of U34 tRNA‐modifying enzymes promotes HIF1α protein synthesis, leading to enhanced glycolysis and conferring mTORC2‐dependent resistance toward targeted BRAF inhibition.
See this image and copyright information in PMC

Comment on

  • Codon-specific translation reprogramming promotes resistance to targeted therapy.
    Rapino F, Delaunay S, Rambow F, Zhou Z, Tharun L, De Tullio P, Sin O, Shostak K, Schmitz S, Piepers J, Ghesquière B, Karim L, Charloteaux B, Jamart D, Florin A, Lambert C, Rorive A, Jerusalem G, Leucci E, Dewaele M, Vooijs M, Leidel SA, Georges M, Voz M, Peers B, Büttner R, Marine JC, Chariot A, Close P. Rapino F, et al. Nature. 2018 Jun;558(7711):605-609. doi: 10.1038/s41586-018-0243-7. Epub 2018 Jun 20. Nature. 2018. PMID: 29925953

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