PMID- 37188809
OWN - NLM
STAT- MEDLINE
DCOM- 20230522
LR  - 20230606
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 13
IP  - 1
DP  - 2023 May 15
TI  - PARP2 poly(ADP-ribosyl)ates nuclear factor erythroid 2-related factor 2 (NRF2) 
      affecting NRF2 subcellular localization.
PG  - 7869
LID - 10.1038/s41598-023-35076-w [doi]
LID - 7869
AB  - PARP2 is a member of the PARP enzyme family. Although, PARP2 plays role in DNA 
      repair, it has regulatory roles in mitochondrial and lipid metabolism, it has 
      pivotal role in bringing about the adverse effects of pharmacological PARP 
      inhibitors. Previously, we showed that the ablation of PARP2 induces oxidative 
      stress and, consequently, mitochondrial fragmentation. In attempt to identify the 
      source of the reactive species we assessed the possible role of a central 
      regulator of cellular antioxidant defense, nuclear factor erythroid 2-related 
      factor 2 (NRF2). The silencing of PARP2 did not alter either the mRNA or the 
      protein expression of NRF2, but changed its subcellular localization, decreasing 
      the proportion of nuclear, active fraction of NRF2. Pharmacological inhibition of 
      PARP2 partially restored the normal localization pattern of NRF2 and in line with 
      that, we showed that NRF2 is PARylated that is absent in the cells in which PARP2 
      was silenced. Apparently, the PARylation of NRF2 by PARP2 has pivotal role in 
      regulating the subcellular (nuclear) localization of NRF2. The silencing of PARP2 
      rearranged the expression of genes encoding proteins with antioxidant function, 
      among these a subset of NRF2-dependent genes.
CI  - (c) 2023. The Author(s).
FAU - Janko, Laura
AU  - Janko L
AD  - Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, 
      Egyetem Ter 1., 4032, Debrecen, Hungary.
AD  - Center of Excellence, The Hungarian Academy of Sciences, Budapest, Hungary.
FAU - Toth, Emese
AU  - Toth E
AD  - Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, 
      Egyetem Ter 1., 4032, Debrecen, Hungary.
AD  - Center of Excellence, The Hungarian Academy of Sciences, Budapest, Hungary.
FAU - Laczik, Miklos
AU  - Laczik M
AD  - Department of Biochemistry and Molecular Biology, Faculty of Medicine, University 
      of Debrecen, Debrecen, 4032, Hungary.
FAU - Rauch, Boglarka
AU  - Rauch B
AD  - Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, 
      Egyetem Ter 1., 4032, Debrecen, Hungary.
AD  - Center of Excellence, The Hungarian Academy of Sciences, Budapest, Hungary.
FAU - Janka, Eszter
AU  - Janka E
AD  - Department of Dermatology, Faculty of Medicine, University of Debrecen, Debrecen, 
      4032, Hungary.
FAU - Balint, Balint L
AU  - Balint BL
AD  - Department of Biochemistry and Molecular Biology, Faculty of Medicine, University 
      of Debrecen, Debrecen, 4032, Hungary.
AD  - Department of Bioinformatics, Semmelweis University, Tuzolto Utca 7-9., Budapest, 
      1094, Hungary.
FAU - Bai, Peter
AU  - Bai P
AD  - Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, 
      Egyetem Ter 1., 4032, Debrecen, Hungary. baip@med.unideb.hu.
AD  - Center of Excellence, The Hungarian Academy of Sciences, Budapest, Hungary. 
      baip@med.unideb.hu.
AD  - MTA-DE Lendulet Laboratory of Cellular Metabolism, Debrecen, 4032, Hungary. 
      baip@med.unideb.hu.
AD  - Research Center for Molecular Medicine, Faculty of Medicine, University of 
      Debrecen, Debrecen, 4032, Hungary. baip@med.unideb.hu.
AD  - MTA-DE Cell Biology and Signaling Research Group ELKH, Debrecen, Hungary. 
      baip@med.unideb.hu.
LA  - eng
SI  - figshare/10.6084/m9.figshare.17127008
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230515
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Antioxidants)
RN  - 0 (NF-E2-Related Factor 2)
SB  - IM
MH  - *Antioxidants
MH  - Cell Nucleus
MH  - DNA Repair
MH  - *NF-E2-Related Factor 2/genetics
MH  - Poly ADP Ribosylation
MH  - Animals
MH  - Mice
PMC - PMC10185692
COIS- The authors declare no competing interests.
EDAT- 2023/05/16 01:09
MHDA- 2023/05/17 06:42
PMCR- 2023/05/15
CRDT- 2023/05/15 23:23
PHST- 2023/01/11 00:00 [received]
PHST- 2023/05/12 00:00 [accepted]
PHST- 2023/05/17 06:42 [medline]
PHST- 2023/05/16 01:09 [pubmed]
PHST- 2023/05/15 23:23 [entrez]
PHST- 2023/05/15 00:00 [pmc-release]
AID - 10.1038/s41598-023-35076-w [pii]
AID - 35076 [pii]
AID - 10.1038/s41598-023-35076-w [doi]
PST - epublish
SO  - Sci Rep. 2023 May 15;13(1):7869. doi: 10.1038/s41598-023-35076-w.