Post-transcriptional regulation of the gli1 oncogene by the expression of alternative 5' untranslated regions

J Biol Chem. 2001 Jan 12;276(2):1311-6. doi: 10.1074/jbc.M005191200.

Abstract

The oncogene GLI1 is involved in the formation of basal cell carcinoma and other tumor types as a result of the aberrant signaling of the Sonic hedgehog-Patched pathway. In this study, we have identified alternative GLI1 transcripts that differ in their 5' untranslated regions (UTRs) and are generated by exon skipping. These are denoted alpha-UTR, beta-UTR, and gamma-UTR according to the number of noncoding exons possessed (three, two, and one, respectively). The alpha- and beta-UTR forms represent the major Gli1 transcripts expressed in mouse tissues, whereas the gamma-UTR is present at relatively low levels but is markedly induced in mouse skin treated with 12-O-tetradecanoylphorbol 13-acetate. Transcripts corresponding to the murine beta and gamma forms were identified in human tissues, but significantly, only the gamma-UTR form was present in basal cell carcinomas and in proliferating cultures of a keratinocyte cell line. Flow cytometry analysis determined that the gamma-UTR variant expresses a heterologous reporter gene 14-23-fold higher than the alpha-UTR and 5-13-fold higher than the beta-UTR in a variety of cell types. Because expression of the gamma-UTR variant correlates with proliferation, consistent with a role for GLI1 in growth promotion, up-regulation of GLI1 expression through skipping of 5' noncoding exons may be an important tumorigenic mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions / genetics
  • Animals
  • Base Sequence
  • COS Cells
  • Carcinoma, Basal Cell / genetics
  • Cells, Cultured
  • Chlorocebus aethiops
  • DNA Primers
  • Exons
  • Gene Expression Regulation*
  • Gene Expression Regulation, Neoplastic
  • Genetic Variation
  • Humans
  • Keratinocytes / metabolism*
  • Mice
  • Molecular Sequence Data
  • Oncogene Proteins / genetics*
  • Oncogene Proteins / metabolism
  • RNA Processing, Post-Transcriptional*
  • Recombinant Fusion Proteins / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Alignment
  • Sequence Homology, Nucleic Acid
  • Trans-Activators
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transcription, Genetic*
  • Transfection
  • Tumor Cells, Cultured
  • Zinc Finger Protein GLI1
  • Zinc Fingers

Substances

  • 5' Untranslated Regions
  • DNA Primers
  • Oncogene Proteins
  • Recombinant Fusion Proteins
  • Trans-Activators
  • Transcription Factors
  • Zinc Finger Protein GLI1