A new APE1/Ref-1-dependent pathway leading to reduction of NF-κB and AP-1, and activation of their DNA-binding activity

Kozue Ando, Satoshi Hirao, Yasuaki Kabe, Yuji Ogura, Iwao Sato, Yuki Yamaguchi, Tadashi Wada, Hiroshi Handa

研究成果: Article査読

104 被引用数 (Scopus)

抄録

APE1/Ref-1 is thought to be a multifunctional protein involved in reduction-oxidation (redox) regulation and base excision DNA repair, and is required for early embryonic development in mice. APE1/Ref-1 has redox activity and AP endonuclease activity, and is able to enhance DNA-binding activity of several transcription factors, including NF-κB, AP-1 and p53, through reduction of their critical cysteine residues. However, it remains elusive exactly how APE1/Ref-1 carries out its essential functions in vivo. Here, we show that APE1/Ref-1 not only reduces target transcription factors directly but also facilitates their reduction by other reducing molecules such as glutathione or thioredoxin. The new activity of APE1/Ref-1, termed redox chaperone activity, is exerted at concentration significantly lower than that required for its redox activity and is neither dependent on its redox activity nor on its AP endonuclease activity. We also show evidence that redox chaperone activity of APE1/Ref-1 is critical to NF-κB-mediated gene expression in human cells and is mediated through its physical association with target transcription factors. Thus, APE1/Ref-1 may play multiple roles in an antioxidative stress response pathway through its different biochemical activities. These findings also provide new insight into the mechanism of intracellular redox regulation.

本文言語English
ページ(範囲)4327-4336
ページ数10
ジャーナルNucleic acids research
36
13
DOI
出版ステータスPublished - 2008 8
外部発表はい

ASJC Scopus subject areas

  • 遺伝学

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