The recent discovery that p53 gene encodes for nine different p53 proteins (isoforms) may have a profound impact on our understanding of p53 tumour suppressor activity.
Multiple p53 variants exists due to alternative promoters and multiple alternative splicing. These variants encode distinct isoforms, which can regulate p53 transcriptional activity .
The intron 9 can be alternatively spliced to produce three isoforms: p53, p53ß (identical to p53i9) and p53γ, where the p53ß and p53γ isoforms lack the oligomerisation domain.
p53 , p53ß, p53γ, ∆133p53, ∆133p53ß and ∆133p53γ – These isoforms due to alternative splicing of the intron 9 and usage of the alternative promoter in intron 4
∆40p53, ∆40p53ß, ∆40p53γ – These isoforms due to alternative splicing of the intron 9 and alternative initiation of translation or alternative splicing of the intron 2.
p53 variant mRNA are expressed in several normal human tissues in a tissue-dependent manner, that could explain the tissue-specific regulation of p53 transcriptional activity in responses to stresses such as ionising radiation, UV, pH and hypoxia.
Studies in several tumour types have shown that the nine different p53 isoforms are abnormally expressed in tumour tissues compared to normal cells. p53 protein isoforms modulate p53 transcriptional activity and cell fate outcome in response to stress.
Fig 3 - Various P53 Isoforms