Gene regulation by temperature-sensitive p53 mutants: identification of p53 response genes

Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10640-4. doi: 10.1073/pnas.91.22.10640.

Abstract

The ability of the p53 protein to act as a sequence-specific transcriptional activator suggests that genes induced by p53 may encode critical mediators of p53 tumor suppression. Using a tetracycline-regulated p53 expression system and cDNA library subtraction procedure, we identified several p53-induced gene transcripts in human Saos-2 osteosarcoma cells that are novel on the basis of their size, regulation, and low abundance. Wild-type p53-dependent induction of these transcripts was observed in cells that are growth arrested by p53, as well as in cells that undergo apoptosis upon expression of an inducible wild-type p53 transgene. These results show that p53 activates the expression of numerous response genes and suggest that multiple effectors may play a role in mediating cellular functions of p53.

MeSH terms

  • Apoptosis
  • Base Sequence
  • Binding Sites
  • Blotting, Northern
  • Blotting, Western
  • Cell Line
  • DNA, Neoplasm / metabolism
  • Gene Expression Regulation, Neoplastic* / drug effects
  • Gene Library
  • Genes, p53
  • Humans
  • Kinetics
  • Luciferases / biosynthesis
  • Molecular Sequence Data
  • Mutagenesis
  • Mutation*
  • Nuclear Proteins / isolation & purification
  • Nuclear Proteins / metabolism
  • Osteosarcoma
  • Plasmids
  • RNA, Messenger / isolation & purification
  • RNA, Messenger / metabolism
  • Temperature
  • Tetracycline / pharmacology
  • Transcription, Genetic
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • DNA, Neoplasm
  • Nuclear Proteins
  • RNA, Messenger
  • Tumor Suppressor Protein p53
  • Luciferases
  • Tetracycline