p73: a multifunctional protein in neurobiology

Mol Neurobiol. 2011 Apr;43(2):139-46. doi: 10.1007/s12035-011-8172-6. Epub 2011 Mar 8.

Abstract

p73, a transcription factor of the p53 family, plays a key role in many biological processes including neuronal development. Indeed, mice deficient for both TAp73 and ΔNp73 isoforms display neuronal pathologies, including hydrocephalus and hippocampal dysgenesis, with defects in the CA1-CA3 pyramidal cell layers and the dentate gyrus. TAp73 expression increases in parallel with neuronal differentiation and its ectopic expression induces neurite outgrowth and expression of neuronal markers in neuroblastoma cell lines and neural stem cells, suggesting that it has a pro-differentiation role. In contrast, ΔNp73 shows a survival function in mature cortical neurons as selective ΔNp73 null mice have reduced cortical thickness. Recent evidence has also suggested that p73 isoforms are deregulated in neurodegenerative pathologies such as Alzheimer's disease, with abnormal tau phosphorylation. Thus, in addition to its increasingly accepted contribution to tumorigenesis, the p73 subfamily also plays a role in neuronal development and neurodegeneration.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Differentiation
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Models, Biological
  • Nerve Degeneration / metabolism
  • Nervous System / metabolism*
  • Nervous System / pathology
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Stem Cells / cytology
  • Tumor Protein p73
  • Tumor Suppressor Proteins / chemistry
  • Tumor Suppressor Proteins / metabolism*

Substances

  • DNA-Binding Proteins
  • Nuclear Proteins
  • Trp73 protein, mouse
  • Tumor Protein p73
  • Tumor Suppressor Proteins
  • delta Np73 protein, human
  • p73 protein, human