P53 talks to PARP: the increasing complexity of p53-induced cell death

Abstract

The p53 tumor suppressor is well known for its ability to trigger cell death by apoptosis or induce cellular senescence. p53 is also involved in a wide range of other biological processes, such as differentiation, metabolism, fecundity, and aging.1, 2 p53 responds to DNA damage, induced by, for instance, gamma irradiation or chemotherapeutic drugs, and triggers cell cycle arrest, DNA repair, apoptosis, or senescence.1, 2 A key function of p53 is to respond to oncogenic stress. Activation of p53 by oncogenic signalling may occur via ARF, an inhibitor of the p53 antagonist Mdm2, or by induction of a DNA damage response that involves activation of ATM, ATR, Chk1, and/or Chk2 kinases. The p53 response to oncogenic stress allows efficient elimination of incipient tumor cells and is fundamental for suppression of tumor development.3 However, p53 is mutated in a large fraction of human tumors, leading to evasion of p53-dependent cell death.4, 5 Restoration of wild-type p53 expression causes rapid elimination of tumors in vivo.6, 7, 8