Telomerase Reverse Transcriptase Gene Is a Direct Target of c-Myc but Is Not Functionally Equivalent in Cellular Transformation

Oncogene. 1999 Feb 4;18(5):1219-26. doi: 10.1038/sj.onc.1202669.

Abstract

The telomerase reverse transcriptase component (TERT) is not expressed in most primary somatic human cells and tissues, but is upregulated in the majority of immortalized cell lines and tumors. Here, we identify the c-Myc transcription factor as a direct mediator of telomerase activation in primary human fibroblasts through its ability to specifically induce TERT gene expression. Through the use of a hormone inducible form of c-Myc (c-Myc-ER), we demonstrate that Myc-induced activation of the hTERT promoter requires an evolutionarily conserved E-box and that c-Myc-ER-induced accumulation of hTERT mRNA takes place in the absence of de novo protein synthesis. These findings demonstrate that the TERT gene is a direct transcriptional target of c-Myc. Since telomerase activation frequently correlates with immortalization and telomerase functions to stabilize telomers in cycling cells, we tested whether Myc-induced activation of TERT gene expression represents an important mechanism through which c-Myc acts to immortalize cells. Employing the rat embryo fibroblast cooperation assay, we show that TERT is unable to substitute for c-Myc in the transformation of primary rodent fibroblasts, suggesting that the transforming activities of Myc extend beyond its ability to activate TERT gene expression and hence telomerase activity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bacterial Proteins / metabolism*
  • Base Sequence
  • Cell Transformation, Neoplastic*
  • Conserved Sequence
  • DNA-Binding Proteins
  • Gene Expression Regulation
  • Humans
  • Mice
  • Molecular Sequence Data
  • Peptidylprolyl Isomerase*
  • Promoter Regions, Genetic
  • Protein Biosynthesis*
  • Proteins / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • RNA*
  • RNA-Directed DNA Polymerase / biosynthesis*
  • RNA-Directed DNA Polymerase / genetics
  • Rats
  • Sequence Homology, Nucleic Acid
  • Telomerase / biosynthesis*
  • Telomerase / genetics
  • Transcription, Genetic

Substances

  • Bacterial Proteins
  • DNA-Binding Proteins
  • Proteins
  • Proto-Oncogene Proteins c-myc
  • telomerase RNA
  • RNA
  • RNA-Directed DNA Polymerase
  • TERT protein, human
  • Telomerase
  • Tert protein, mouse
  • ILPA protein, Aeromonas hydrophila
  • Peptidylprolyl Isomerase

Associated data

  • GENBANK/AF121948
  • GENBANK/AF121949