p73: A Multifunctional Protein in Neurobiology

p73, a transcription factor of the p53 family,plays a key role in many biological processes includingneuronal development. Indeed, mice deficient for bothTAp73 and ΔNp73 isoforms display neuronal pathologies,including hydrocephalus and hippocampal dysgenesis, withdefects in the CA1-CA3 pyramidal cell layers and thedentate gyrus. TAp73 expression increases in parallel withneuronal differentiation and its ectopic expression inducesneurite outgrowth and expression of neuronal markers inneuroblastoma cell lines and neural stem cells, suggestingthat it has a pro-differentiation role. In contrast, ΔNp73shows a survival function in mature cortical neurons asselective ΔNp73 null mice have reduced cortical thickness.Recent evidence has also suggested that p73 isoforms arederegulated in neurodegenerative pathologies such asAlzheimer’s disease, with abnormal tau phosphorylation.Thus, in addition to its increasingly accepted contributionto tumorigenesis, the p73 subfamily also plays a role inneuronal development and neurodegeneration.