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

Paul O Hassa1

  • 1European Molecular Biology Laboratory (EMBL), Gene Expression Unit, Meyerhofstrasse 1, D-69117 Heidelberg, Germany. phassa9@googlemail.com

Frontiers in Bioscience (Landmark Edition)
|March 11, 2009
PubMed

Insights

Poly(ADP-ribose) polymerases (PARP1 and PARP2) exhibit a dual role in cell fate, mediating both cell death and survival. Understanding this duality is crucial for cellular stress response research.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Poly(ADP-ribose) polymerases (PARP1 and PARP2) are critical regulators of cellular responses to stress.
  • Overactivation of PARP1 is implicated in programmed necrotic cell death.
  • PARP1 also participates in other cell death pathways like apoptosis and macroautophagy.

Purpose of the Study:

  • To review recent findings on the pivotal role of PARP1 in programmed cell death and cell survival.
  • To elucidate the molecular mechanisms behind PARP1's dual "Jekyll and Hyde" function.
  • To discuss potential crosstalk between PARP1, PARP2, and other NAD+-dependent ADP-ribosylating enzymes.

Main Methods:

  • Literature review of genetic and pharmacological studies.
  • Analysis of in vivo data on cell death and survival.
  • Exploration of molecular mechanisms and enzyme interactions.

Main Results:

  • PARP1 and PARP2 are essential for maintaining genomic integrity.
  • These enzymes act as survival factors for proliferating cells (e.g., stem cells) and non-proliferating neurons against oxidative stress.
  • Evidence supports a crucial, albeit complex, role for PARP1 in diverse cell fate pathways.

Conclusions:

  • PARP1 and PARP2 display a paradoxical role, promoting cell death under certain conditions and survival under others.
  • The "Jekyll and Hyde" duality of PARP1 is central to its function in cell death and survival.
  • Interactions with enzymes like Sirtuins and CD38 may further modulate these pathways.

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