p53 protein variants: structural and functional similarities with p63 and p73 isoforms

Since its discovery in 1979, many studies have reported that the p53 tumour suppressor protein could be expressed in the form of products smaller than those predicted by the full-length amino-acid sequence. These products differ from full-length p53 in their N- or C-terminal regions, but generally conserve the central, DNA-binding domain. They appear to be expressed at rather low levels and to be restricted to particular cell types and/or physiological circumstances, suggesting that they play very narrow and specific roles. Several mechanisms have been proposed to explain their timely occurrence, including alternative splicing, internal initiation of translation or proteolytic cleavage. A precise assessment of the various 'p53 isoforms' reveals striking similarities with several isoforms of the p53 homologous proteins p63 or p73, suggesting that regulated production of specific, N- or C-terminal variants may be a 'trademark' of all family members. In this review, we summarize the published evidence on the structure, mode of production, expression and function of the p53 isoforms, and discuss their properties in the light of recent data on the structure and function of p63/p73 isoforms.