An anti-apoptotic role for the p53 family member, p73, during developmental neuron death

Science. 2000 Jul 14;289(5477):304-6. doi: 10.1126/science.289.5477.304.

Abstract

p53 plays an essential pro-apoptotic role, a function thought to be shared with its family members p73 and p63. Here, we show that p73 is primarily present in developing neurons as a truncated isoform whose levels are dramatically decreased when sympathetic neurons apoptose after nerve growth factor (NGF) withdrawal. Increased expression of truncated p73 rescues these neurons from apoptosis induced by NGF withdrawal or p53 overexpression. In p73-/- mice, all isoforms of p73 are deleted and the apoptosis of developing sympathetic neurons is greatly enhanced. Thus, truncated p73 is an essential anti-apoptotic protein in neurons, serving to counteract the pro-apoptotic function of p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Apoptosis / physiology*
  • Cells, Cultured
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / physiology*
  • Escherichia coli
  • Genes, Tumor Suppressor
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Nerve Growth Factor / pharmacology
  • Neurons / physiology*
  • Nuclear Proteins / biosynthesis
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / physiology*
  • Protein Isoforms / biosynthesis
  • Protein Isoforms / chemistry
  • Protein Isoforms / physiology
  • Recombinant Proteins
  • Sympathetic Nervous System / cytology
  • Sympathetic Nervous System / physiology*
  • Tumor Protein p73
  • Tumor Suppressor Protein p53 / antagonists & inhibitors
  • Tumor Suppressor Protein p53 / physiology*
  • Tumor Suppressor Proteins

Substances

  • DNA-Binding Proteins
  • Nuclear Proteins
  • Protein Isoforms
  • Recombinant Proteins
  • TP73 protein, human
  • Trp73 protein, mouse
  • Tumor Protein p73
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • Nerve Growth Factor