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PARP2 poly(ADP-ribosyl)ates nuclear factor erythroid 2-related factor 2 (NRF2) affecting NRF2 subcellular

Laura Jankó1,2, Emese Tóth1,2, Miklós Laczik3

  • 1Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Egyetem Tér 1., 4032, Debrecen, Hungary.

Scientific Reports
|May 15, 2023
PubMed

Insights

Poly (ADP-ribose) polymerase 2 (PARP2) regulates nuclear factor erythroid 2-related factor 2 (NRF2) localization. PARP2 inhibition disrupts NRF2

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cellular Biology

Background:

  • Poly (ADP-ribose) polymerase 2 (PARP2) is involved in DNA repair and metabolism.
  • PARP2 contributes to adverse effects of PARP inhibitors.
  • PARP2 deficiency causes oxidative stress and mitochondrial fragmentation.

Purpose of the Study:

  • To investigate the role of PARP2 in regulating cellular antioxidant defense.
  • To identify the source of reactive species in PARP2-deficient cells.
  • To elucidate the mechanism by which PARP2 influences nuclear factor erythroid 2-related factor 2 (NRF2) localization.

Main Methods:

  • Gene silencing of PARP2.
  • Assessment of NRF2 mRNA and protein expression.
  • Analysis of NRF2 subcellular localization.
  • Pharmacological inhibition of PARP2.
  • Investigation of NRF2 PARylation.
  • Gene expression analysis of antioxidant and NRF2-dependent genes.

Main Results:

  • PARP2 silencing altered NRF2 subcellular localization, decreasing nuclear NRF2.
  • Pharmacological PARP2 inhibition partially restored NRF2 localization.
  • NRF2 is PARylated by PARP2, a process absent in PARP2-silenced cells.
  • PARP2 regulates NRF2 nuclear localization through PARylation.
  • PARP2 deficiency altered the expression of antioxidant and NRF2-dependent genes.

Conclusions:

  • PARP2 plays a critical role in regulating NRF2 nuclear localization via PARylation.
  • PARP2 influences cellular antioxidant defense by modulating NRF2 activity.
  • Understanding PARP2-NRF2 interaction is crucial for managing PARP inhibitor side effects and cellular redox homeostasis.

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