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Oncogene. 2017 Nov 23;36(47):6640-6648. doi: 10.1038/onc.2017.273. Epub 2017 Aug 7.

Short stretches of rare codons regulate translation of the transcription factor ZEB2 in cancer cells.

Author information

1
Department of Cancer Studies, University of Leicester, Leicester, UK.
2
MRC Toxicology Unit, Leicester, UK.
3
Protein and Nucleic Acid Chemistry Laboratory (PNACL), University of Leicester, Leicester, UK.
4
Cancer Sciences Division, University of Southampton, Southampton, UK.

Abstract

Two proteins comprising the ZEB family of zinc finger transcription factors, ZEB1 and ZEB2, execute EMT programs in embryonic development and cancer. By studying regulation of their expression, we describe a novel mechanism that limits ZEB2 protein synthesis. A protein motif located at the border of the SMAD-binding domain of ZEB2 protein induces ribosomal pausing and compromises protein synthesis. The function of this protein motif is dependent on stretches of rare codons, Leu(UUA)-Gly(GGU)-Val(GUA). Incorporation of these triplets in the homologous region of ZEB1 does not affect protein translation. Our data suggest that rare codons have a regulatory role only if they are present within appropriate protein structures. We speculate that pools of transfer RNA available for protein translation impact on the configuration of epithelial mesenchymal transition pathways in tumor cells.

PMID:
28783176
PMCID:
PMC5681250
DOI:
10.1038/onc.2017.273
[Indexed for MEDLINE]
Free PMC Article

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