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

W. R. Wan Makhtar, G. Browne, A. Karountzos, C. Stevens, Y. Alghamdi, A. R. Bottrill, S. Mistry, E. Smith, M. Bushel, J. H. Pringle, A. E. Sayan, E. Tulchinsky

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Two proteins comprising the ZEB family of zinc finger transcripton 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.

Original languageEnglish
Pages (from-to)6640-6648
Number of pages9
JournalOncogene
Volume36
Issue number47
DOIs
Publication statusPublished - Nov 23 2017
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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