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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
Summary
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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