Top

Minireview

Split Viewer

Mol. Cells 2009; 27(3): 279-282

Published online March 31, 2009

https://doi.org/10.1007/s10059-009-0050-y

© The Korean Society for Molecular and Cellular Biology

Transcriptional Regulation of the AP-1 and Nrf2 Target Gene Sulfiredoxin

Francesc X. Soriano, Paul Baxter, Lyndsay M. Murray, Michael B. Sporn, Thomas H. Gillingwater, and Giles E. Hardingham

Received: February 12, 2009; Accepted: February 15, 2009

Abstract

Two-cysteine” peroxiredoxins are antioxidant enzymes that exert a cytoprotective effect in many models of oxidative stress. However, under highly oxidizing conditions they can be inactivated through hyperoxidation of their peroxidatic active site cysteine residue. Sulfiredoxin can reverse this hyperoxidation, thus reactivating peroxiredoxins. Here we review recent investigations that have shed further light on sulfiredoxin’s role and regulation. Studies have revealed sulfiredoxin to be a dynamically regulated gene whose transcription is induced by a variety of signals and stimuli. Sulfiredoxin expression is regulated by the transcription factor AP-1, which mediates its up-regulation by synaptic activity in neurons, resulting in protection against oxidative stress. Furthermore, sulfiredoxin has been identified as a new member of the family of genes regulated by Nuclear factor erythroid 2-related factor (Nrf2) via a conserved cis-acting antioxidant response element (ARE). As such, sulfiredoxin is likely to contribute to the net antioxidative effect of small molecule activators of Nrf2. As discussed here, the proximal AP-1 site of the sulfiredoxin promoter is embedded within the ARE, as is common with Nrf2 target genes. Other recent studies have shown that sulfiredoxin induction via Nrf2 may form an important part of the protective response to oxidative stress in the lung, preventing peroxiredoxin hyperoxidation and, in certain cases, subsequent degradation. We illustrate here that sulfiredoxin can be rapidly induced in vivo by administration of CDDO-TFEA, a synthetic triterpenoid inducer of endogenous Nrf2, which may offer a way of reversing peroxiredoxin hyperoxidation in vivo following chronic or acute oxidative stress.

Keywords antioxidant response element, AP-1, Nrf2, oxidative stress, peroxiredoxin, sulfiredoxin

Article

Minireview

Mol. Cells 2009; 27(3): 279-282

Published online March 31, 2009 https://doi.org/10.1007/s10059-009-0050-y

Copyright © The Korean Society for Molecular and Cellular Biology.

Transcriptional Regulation of the AP-1 and Nrf2 Target Gene Sulfiredoxin

Francesc X. Soriano, Paul Baxter, Lyndsay M. Murray, Michael B. Sporn, Thomas H. Gillingwater, and Giles E. Hardingham

Received: February 12, 2009; Accepted: February 15, 2009

Abstract

Two-cysteine” peroxiredoxins are antioxidant enzymes that exert a cytoprotective effect in many models of oxidative stress. However, under highly oxidizing conditions they can be inactivated through hyperoxidation of their peroxidatic active site cysteine residue. Sulfiredoxin can reverse this hyperoxidation, thus reactivating peroxiredoxins. Here we review recent investigations that have shed further light on sulfiredoxin’s role and regulation. Studies have revealed sulfiredoxin to be a dynamically regulated gene whose transcription is induced by a variety of signals and stimuli. Sulfiredoxin expression is regulated by the transcription factor AP-1, which mediates its up-regulation by synaptic activity in neurons, resulting in protection against oxidative stress. Furthermore, sulfiredoxin has been identified as a new member of the family of genes regulated by Nuclear factor erythroid 2-related factor (Nrf2) via a conserved cis-acting antioxidant response element (ARE). As such, sulfiredoxin is likely to contribute to the net antioxidative effect of small molecule activators of Nrf2. As discussed here, the proximal AP-1 site of the sulfiredoxin promoter is embedded within the ARE, as is common with Nrf2 target genes. Other recent studies have shown that sulfiredoxin induction via Nrf2 may form an important part of the protective response to oxidative stress in the lung, preventing peroxiredoxin hyperoxidation and, in certain cases, subsequent degradation. We illustrate here that sulfiredoxin can be rapidly induced in vivo by administration of CDDO-TFEA, a synthetic triterpenoid inducer of endogenous Nrf2, which may offer a way of reversing peroxiredoxin hyperoxidation in vivo following chronic or acute oxidative stress.

Keywords: antioxidant response element, AP-1, Nrf2, oxidative stress, peroxiredoxin, sulfiredoxin

Mol. Cells
Jun 30, 2022 Vol.45 No.6, pp. 353~434
COVER PICTURE
ERα is modified by UFM1 and this modification (ufmylation) plays a crucial role in promoting the stability of ERα and breast cancer development. However, when ERα is deufmylated and then ubiquitinated, it disappears by proteasome-mediated degradation (Yoo et al., pp. 425-434).

Share this article on

  • line
  • mail

Related articles in Mol. Cells

Molecules and Cells

eISSN 0219-1032
qr-code Download