Cancer chemotherapeutic agents such as cisplatin exert their cytotoxic effect by 
inducing DNA damage and activating programmed cell death (apoptosis). The 
tumour-suppressor protein p53 is an important activator of apoptosis. Although 
p53-deficient cancer cells are less responsive to chemotherapy, their resistance 
is not complete, which suggests that other apoptotic pathways may exist. A 
p53-related gene, p73, which encodes several proteins as a result of alternative 
splicing, can also induce apoptosis. Here we show that the amount of p73 protein 
in the cell is increased by cisplatin. This induction of p73 is not seen in 
cells unable to carry out mismatch repair and in which the nuclear enzyme c-Abl 
tyrosine kinase is not activated by cisplatin. The half-life of p73 is prolonged 
by cisplatin and by co-expression with c-Abl tyrosine kinase; the 
apoptosis-inducing function of p73 is also enhanced by the c-Abl kinase. Mouse 
embryo fibroblasts deficient in mismatch repair or in c-Abl do not upregulate 
p73 and are more resistant to killing by cisplatin. Our results indicate that 
c-Abl and p73 are components of a mismatch-repair-dependent apoptosis pathway 
which contributes to cisplatin-induced cytotoxicity.