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PMID: 1380454 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Redox activation of Fos-Jun DNA binding activity is mediated by a DNA repair enzyme.

The EMBO journal ·Vol. 11 ·No. 9 ·1992-09-00 ·Pages 3323-35

Xanthoudakis S, Miao G, Wang F, Pan YC, Curran T

Abstract

The DNA binding activity of Fos and Jun is regulated in vitro by a post-translational mechanism involving reduction-oxidation. Redox regulation occurs through a conserved cysteine residue located in the DNA binding domain of Fos and Jun. Reduction of this residue by chemical reducing agents or by a ubiquitous nuclear redox factor (Ref-1) recently purified from Hela cells, stimulates AP-1 DNA binding activity in vitro, whereas oxidation or chemical modification of the cysteine has an inhibitory effect on DNA binding activity. Here we demonstrate that the protein product of the ref-1 gene stimulates the DNA binding activity of Fos-Jun heterodimers, Jun-Jun homodimers and Hela cell AP-1 proteins as well as that of several other transcription factors including NF-kappa B, Myb and members of the ATF/CREB family. Furthermore, immunodepletion analysis indicates that Ref-1 is the major AP-1 redox activity in Hela nuclear extracts. Interestingly, Ref-1 is a bifunctional protein; it also possesses an apurinic/apyrimidinic (AP) endonuclease DNA repair activity. However, the redox and DNA repair activities of Ref-1 can, in part, be distinguished biochemically. This study suggests a novel link between transcription factor regulation, oxidative signalling and DNA repair processes in higher eukaryotes.

Related Genes
ref-1
MeSH Terms
Amino Acid Sequence Animals Base Sequence Cloning, Molecular DNA/metabolism DNA Repair/physiology DNA-(Apurinic or Apyrimidinic Site) Lyase DNA-Binding Proteins/metabolism Deoxyribonuclease IV (Phage T4-Induced) Endodeoxyribonucleases/genetics,metabolism Escherichia coli Escherichia coli Proteins Fluorescent Antibody Technique HeLa Cells Humans Molecular Sequence Data Nuclear Proteins/genetics,isolation & purification,metabolism Oxidation-Reduction Proto-Oncogene Proteins c-fos/metabolism Proto-Oncogene Proteins c-jun/metabolism Saccharomyces cerevisiae Proteins Sequence Homology, Nucleic Acid Trans-Activators Transcription Factors/metabolism
Chemicals
DNA-Binding Proteins Escherichia coli Proteins HAP1 protein, S cerevisiae Nuclear Proteins Proto-Oncogene Proteins c-fos Proto-Oncogene Proteins c-jun Saccharomyces cerevisiae Proteins Trans-Activators Transcription Factors DNA Endodeoxyribonucleases Deoxyribonuclease IV (Phage T4-Induced) endonuclease IV, E coli APEX1 protein, human DNA-(Apurinic or Apyrimidinic Site) Lyase
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Xanthoudakis S
Department of Molecular Oncology and Virology, Roche Institute of Molecular Biology, New York, NY.
Miao G
Wang F
Pan Y C
Curran T
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1992-09-00
Pages
3323-35
Language
English
Region
England
NLM ID
8208664
PMCID
PMC556867
Subset
IM
Databases
GENBANK
S43127, X66121, X66358, X66359, X66360, X66361, X66362, X66363, X66364, X66365
External Links
PubMed source PMC Full Text View journal details
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