Poly(ADP-ribose) polymerase-1 modulates Nrf2-dependent transcription

Tongde Wu, Xiao Jun Wang, Wang Tian, Melba C. Jaramillo, Alexandria Lau, Donna D. Zhang

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

The basic leucine zipper transcription factor Nrf2 has emerged as a master regulator of intracellular redox homeostasis by controlling the expression of a battery of redox-balancing antioxidants and phase II detoxification enzymes. Under oxidative stress conditions, Nrf2 is induced at the protein level through redox-sensitive modifications on critical cysteine residues in Keap1, a component of an E3 ubiquitin ligase complex that targets Nrf2 for proteasomal degradation. Poly(ADP-ribose) polymerase-1 (PARP-1) is historically known to function in DNA damage detection and repair; however, recently PARP-1 has been shown to play an important role in other biochemical activities, such as DNA methylation and imprinting, insulator activity, chromosome organization, and transcriptional regulation. The exact role of PARP-1 in transcription modulation and the underlying mechanisms remain poorly defined. In this study, we report that PARP-1 forms complexes with the antioxidant response element (ARE) within the promoter region of Nrf2 target genes and upregulates the transcriptional activity of Nrf2. Interestingly, PARP-1 neither physically interacts with Nrf2 nor promotes the expression of Nrf2. In addition, PARP-1 does not target Nrf2 for poly(ADP-ribosyl)ation. Instead, PARP-1 interacts directly with small Maf proteins and the ARE of Nrf2 target genes, which augments ARE-specific DNA-binding of Nrf2 and enhances the transcription of Nrf2 target genes. Collectively, these results suggest that PARP-1 serves as a transcriptional coactivator, upregulating the transcriptional activity of Nrf2 by enhancing the interaction among Nrf2, MafG, and the ARE.

Original languageEnglish (US)
Pages (from-to)69-80
Number of pages12
JournalFree Radical Biology and Medicine
Volume67
DOIs
StatePublished - 2014

Keywords

  • ARE
  • Free radicals
  • Maf
  • Nrf2
  • PARP-1
  • Transcriptional coactivator

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Poly(ADP-ribose) polymerase-1 modulates Nrf2-dependent transcription'. Together they form a unique fingerprint.

  • Cite this