The role of truncated p53 isoforms in the DNA damage response

Abstract

The tumour suppressor p53 is activated following genotoxic stress and regulates the expression of target genes involved in the DNA damage response (DDR). The discovery that p53 isoforms alter the transcription of p53 target genes or p53 protein interactions unveiled an alternative DDR. This review will focus on the role p53 isoforms play in response to DNA damage. The expression of the C-terminally truncated p53 isoforms may be modulated via DNA damage-induced alternative splicing, whereas alternative translation plays an important role in modulating the expression of N-terminally truncated isoforms. The DDR induced by p53 isoforms may enhance the canonical p53 DDR or block cell death mechanisms in a DNA damage- and cell-specific manner, which could contribute to chemoresistance in a cancer context. Thus, a better understanding of the involvement of p53 isoforms in the cell fate decisions could uncover potential therapeutic targets in cancer and other diseases.

Keywords: Cell death; DNA damage response; DNA repair; Genotoxic stress; TP53.