p73 in apoptosis

Apoptosis. 2001 Dec;6(6):447-52. doi: 10.1023/a:1012433522902.

Abstract

The TP53 tumour-suppressor gene belongs to a family that includes the two recently identified homologues TP63 and TP73. Overexpression of p73 can activate typical p53-responsive genes and induce apoptosis like p53. In addition, activation of p73 has been implicated in apoptotic cell death induced by aberrant cell proliferation and some forms of DNA-damage. These data together with the localization of TP73 on chromosome 1p36, a region frequently deleted in a variety of human cancers, led to the hypothesis that p73 has tumour suppressor activity just like p53. However, despite its proapoptotic activity in vitro, the lack of tumour-formation in p73 knock-out mice and primary human tumour data demonstrating overexpression of wild-type p73 currently argue against p73 being a classical tumour suppressor. Interestingly, in contrast to TP53, TP73 gives rise to a complex pattern of pro- and antiapoptotic p73 isoforms generated by differential splicing and alternative promoter usage. Therefore further insight into the function and regulation of these structurally and functionally diverse p73 proteins is needed to elucidate the role of TP73 for apoptosis and human tumorigenesis.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis*
  • Chromosomes, Human, Pair 1
  • DNA Damage
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism*
  • DNA-Binding Proteins / physiology
  • Genes, Tumor Suppressor
  • Humans
  • Models, Biological
  • Neoplasms / metabolism
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism*
  • Nuclear Proteins / physiology
  • Protein Binding
  • Protein Isoforms
  • Signal Transduction
  • Tumor Protein p73
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Suppressor Proteins

Substances

  • DNA-Binding Proteins
  • Nuclear Proteins
  • Protein Isoforms
  • Trp73 protein, mouse
  • Tumor Protein p73
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • p73 protein, human