Direct regulation of RNA polymerase III transcription by RB, p53 and c-Myc

Cell Cycle. May-Jun 2003;2(3):181-4.

Abstract

The synthesis of tRNA and 5S rRNA by RNA polymerase (pol) III is cell cycle regulated in higher organisms. Overexpression of pol III products is a general feature of transformed cells. These observations may be explained by the fact that a pol III-specific transcription factor, TFIIIB, is strongly regulated by the tumor suppressors RB and p53, as well as the proto-oncogene product c-Myc. RB and p53 repress TFIIIB, but this restraint can be lost in tumors through a variety of mechanisms. In contrast, c-Myc binds and activates TFIIIB, causing potent induction of pol III transcription. Using chromatin immunoprecipitation and RNA interference, we show that c-Myc interacts with tRNA and 5S rRNA genes in transformed cervical cells, stimulating their expression. Availability of pol III products may be an important determinant of a cell's capacity to grow. The ability to regulate pol III output may therefore be integral to the growth control functions of RB, p53 and c-Myc.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Division / genetics*
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism*
  • DNA Polymerase III / genetics
  • DNA Polymerase III / metabolism*
  • Eukaryotic Cells / enzymology*
  • Humans
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • RNA / genetics
  • Retinoblastoma Protein / genetics
  • Retinoblastoma Protein / metabolism*
  • Transcription, Genetic / genetics
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Proto-Oncogene Proteins c-myc
  • Retinoblastoma Protein
  • Tumor Suppressor Protein p53
  • RNA
  • DNA Polymerase III