Mechanism of p53 activation in senescent cells

Mammalian chromosomes have telomeres at their ends. Telomere-shortened cells show p53-dependent irreversible cell cycle arrest, but it is still unknown how p53 is activated in telomere-shortened cells. We observed that phosphorylation level of p53 induced in telomere-shortened normal human diploid cells. This phosphorylated p53 formed nuclear foci, and it did not co-localize with TRF2, which is a protein binds to telomeric DNA. We also detected foci of phosphorylated H2AX, but they did not co-localize with TRF2. Furthermore Ser15 phosphorylation was suppressed by wortmannin, an ATM kinase inhibitor. These results suggest that p53 is activated through phosphorylation by ATM-dependent DNA damage checkpoint pathway. (author)