Post-transcriptional regulation of the human transforming growth factor- β1 gene

S. J. Kim, K. Park, D. Koeller, K. Y. Kim, L. M. Wakefield, M. B. Sporn, A. B. Roberts

Research output: Contribution to journalArticle

143 Scopus citations

Abstract

Since many lines of evidence suggest that expression of the transforming growth factor-β1 (TGF-β1) gene may be regulated post-transcriptionally, we examined the effect of the 5'-untranslated region (UTR) of this gene on TGF- β1 expression. For this purpose, fragments of the 840-nucleotide highly GC- rich TGF-β1 5'-UTR were inserted into the 5'-UTR of the structural gene for human growth hormone driven by the simian virus 40 early promoter. A portion of the 5'-UTR of TGF-β1 mRNA spanning the sequences from +11 to +147 was shown to inhibit growth hormone expression by as much as 22-fold. This effect was cell-specific; growth hormone production was inhibited in PC-3 human prostate adenocarcinoma and A-549 human lung adenocarcinoma cells, while no effect was seen in rat pheochromocytoma PC12 cells, which show efficient translation of endogenous TGF-β1 mRNA. Computer analysis showed that this region of the 5'-UTR contained a stable secondary stem-loop structure spanning sequences +49 to +76. This stem-loop region alone is sufficient to inhibit expression of the growth hormone gene, suggesting that it plays an important role in post-transcriptional regulation of TGF-β1 gene expression.

Original languageEnglish (US)
Pages (from-to)13702-13707
Number of pages6
JournalJournal of Biological Chemistry
Volume267
Issue number19
StatePublished - Jan 1 1992

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Kim, S. J., Park, K., Koeller, D., Kim, K. Y., Wakefield, L. M., Sporn, M. B., & Roberts, A. B. (1992). Post-transcriptional regulation of the human transforming growth factor- β1 gene. Journal of Biological Chemistry, 267(19), 13702-13707.