The molecular Jekyll and Hyde duality of PARP1 in cell death and cell survival

The current literature clearly indicates that PARP1 but also PARP2 play a pivotal role in modulating the cellular responses to stress. Genetic and pharmacological studies demonstrated that overactivation of PARP1 is a key mediator of programmed-necrotic cell death in vivo. PARP1 appears to be also involved in programmed cell death processes others than necrosis, such as apoptosis or macroautophagocytotic cell death. On the other hand, growing evidence suggests that both PARP1 and PARP2 are multi-faced enzymes also playing important roles in cell survival processes. PARP1 and PARP2 were shown to be required for the maintenance of genomic integrity and to act as a survival factor for highly proliferating cells such as stem cells but also non-proliferating neuronal cells against cell death induced by oxidative stress under mild and moderate progressive damage in vivo. This review briefly summarizes the recent findings, which support a crucial role of PARP1 in different programmed cell death and cell survival processes. A special focus is placed on the proposed molecular mechanisms underlying the Jekyll and Hyde duality of PARP1 in cell death and cell survival pathways. A potential crosstalk between PARP1, PARP2 and other NAD(+-)dependent ADP-ribosyling enzymes such as Sirtuins and CD38 in cell death and survival pathways is discussed.