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Redox Regulation of Ap-1

A Link between Transcription Factor Signaling and DNA Repair
  • Steven Xanthoudakis
  • Tom Curran
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 387)

Abstract

The inducible transcription factor, AP-1, is a heterodimeric leucine zipper complex containing the protein products of thefos and jun protooncogenes. The DNA binding activity of Fos and Jun is regulated in vitro by a posttranslational mechanism involving reduction-oxidation. Redox regulation is mediated through a conserved cysteine residue located in the DNA binding domain of both proteins. Oxidation or chemical modification of the cysteine has an inhibitory effect on AP-1 DNA binding activity. Conversely, reduction of this residue by chemical reducing agents or by a ubiquitous nuclear redox factor (Ref-1), purified and cloned from human cells, stimulates AP-1 DNA binding activity. In addition, recombinant Ref-1 stimulates the DNA binding activity of several other classes of redox regulated transcription factors. Immunodepletion studies indicate that Ref-1 is the major AP-1 redox activity in Hela cells. Interestingly, Ref-1 is a bifunctional protein; it also possesses an apurinic/apyrimidinic (A/P) endonuclease DNA repair activity. However, the redox and DNA repair activities of Ref-1 are physically and biochemically distinguishable. Ref-1 may represent a novel component of the signal transduction processes that regulate eukaryotic gene expression in response to cellular stress.

Keywords

Redox Activity Redox Regulation Signal Transduction Process Leucine Zipper Domain Eukaryotic Gene Expression 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Steven Xanthoudakis
    • 1
  • Tom Curran
    • 2
  1. 1.Department of CNSNeurogenetics ProgramNutleyUSA
  2. 2.The Roche Institute of Molecular BiologyHoffmann-La Roche Inc.NutleyUSA

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