p53β isoform modulates differentially p53 transcriptional activity in response to stress

We recently established that the p53 gene expresses nine different p53 protein isoforms. The p53 isoforms bind preferentially to some p53-responsive promoters and modulate differentially p53 transcriptional activity [1]. We characterized further p53β activity. p53β is differentially recruited to p21 and bax promoters in the absence or in the presence of DNA-damaging drugs.

p53β enhances p53 transcriptional activity on the p21 promoter in a dose-dependent manner in the absence of cellular stress but inhibits p53 transcriptional activity on the p21 promoter in the presence of DNA-damaging agents. On the contrary, p53β has no effect on p53 transcriptional activity on the bax promoter in the absence of stress but enhances p53 transcriptional activity on the bax promoter in response to stress without increasing the p53 protein level.

Our data indicate that p53β is involved in the choice of p53 target gene expression in response to cellular signals, switching cell fate outcome from G₁ arrest/DNA repair to cell death.

The present finding supports our hypothesis that differential expression of the p53 isoforms in primary breast tumours may help to link p53 status to biological properties and drug sensitivity.