p51A (TAp63gamma), a p53 homolog, accumulates in response to DNA damage for cell regulation

Oncogene. 2000 Jun 22;19(27):3126-30. doi: 10.1038/sj.onc.1203644.

Abstract

p51A, or TAp63gamma, a translation product of gene p51, or p63, was identified as a homolog of p53 in its primary structure and transactivating function. p53 plays a decision-making role in inducing either cell cycle arrest or apoptosis in response to DNA damage, and thereby preserves genome integrity of living cells. To compare the biological activities between p51A and p53, cell lines with low-level, constitutive expression of each protein were obtained by cDNA transfection of mouse erythroleukemic cells. Production of p51A with an apparent molecular mass of 57-kilodalton (kD) accompanied induction of p21waf1 and appearance of hemoglobin-producing cells. After DNA-damaging treatment either with ultraviolet light (UV) irradiation or with actinomycin D, the p51A protein accumulated in time courses corresponding to those of wild-type p53, and caused an increase in the hemoglobin-positive cell count. In contrast, p53-accumulated cells underwent apoptosis without exhibiting the feature of erythroid differentiation. The mode of p21waf1 and Bax-alpha upregulations varied between p51A- and p53-expressing cells and between the types of DNA damage. These results suggest the possibility that p51A induces differentiation under genotoxic circumstances. There may be cellular factors that control p51A protein stability and transactivating ability.

MeSH terms

  • Animals
  • Apoptosis
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / metabolism*
  • DNA Damage*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Dactinomycin / pharmacology
  • Genes, Tumor Suppressor
  • Genes, p53 / physiology*
  • Hemoglobins / metabolism
  • Leukemia, Erythroblastic, Acute
  • Mice
  • Phosphoproteins*
  • Protein Synthesis Inhibitors / pharmacology
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2*
  • Trans-Activators*
  • Transcription Factors
  • Transcriptional Activation
  • Transfection
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / radiation effects
  • Tumor Suppressor Protein p53 / metabolism*
  • Tumor Suppressor Proteins
  • Ultraviolet Rays
  • Up-Regulation
  • bcl-2-Associated X Protein

Substances

  • Bax protein, mouse
  • Cdkn1a protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • DNA-Binding Proteins
  • Hemoglobins
  • Phosphoproteins
  • Protein Synthesis Inhibitors
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • TP63 protein, human
  • Trans-Activators
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • bcl-2-Associated X Protein
  • Dactinomycin