The potential tumor suppressor p73 differentially regulates cellular p53 target genes

Cancer Res. 1998 Nov 15;58(22):5061-5.

Abstract

p73, a potential tumor suppressor, is a p53 homologue. Transient over expression of p73 in cells can induce apoptosis and p21, a cellular p53 target gene primarily responsible for p53-dependent cell cycle arrest. To further characterize the role of p73 in tumor suppression, we established several groups of cell lines that inducibly express p73 under a tetracycline-regulated promoter. By using these cell lines, we found that p73 can induce both cell cycle arrest and apoptosis. We also found that p73 can activate some but not all of the previously identified p53 cellular target genes. Furthermore, we found that the transcriptional activities of p53, p73 alpha, and p73 beta to induce their common cellular target genes differ among one another. These results suggest that p73 is both similar to and different from p53 in their signaling pathways leading to tumor suppression.

Publication types

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

MeSH terms

  • Apoptosis / genetics*
  • Cell Cycle / genetics*
  • Cell Division
  • Cell Line
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / metabolism
  • DNA-Binding Proteins / genetics*
  • G1 Phase / genetics
  • GADD45 Proteins
  • Gene Expression Regulation
  • Genes, Tumor Suppressor / physiology*
  • Genes, p53 / physiology
  • Immediate-Early Proteins / metabolism
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins / genetics*
  • Plasmids
  • Proteins / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2*
  • Proto-Oncogene Proteins c-mdm2
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor
  • S Phase / genetics
  • Signal Transduction
  • Tumor Protein p73
  • Tumor Suppressor Proteins
  • bcl-2-Associated X Protein

Substances

  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • DNA-Binding Proteins
  • Immediate-Early Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor
  • Tumor Protein p73
  • Tumor Suppressor Proteins
  • bcl-2-Associated X Protein
  • Proto-Oncogene Proteins c-mdm2