Cooperative activity of Ref-1/APE and ERp57 in reductive activation of transcription factors.
ERp57, a protein disulfide isomerase localized mainly in the endoplasmic reticulum, has also been found in lesser amounts in the cytosol and nucleus, where its function is still not characterized. We report here that ERp57 displays affinity for Ref-1, a protein involved in DNA repair as well as in the reduction and activation of transcription factors. Immunoprecipitation experiments showed that Ref-1 and ERp57 also interact in vivo in at least three types of cultured human cells, namely HepG2, M14, and Raji. Oxidative stress increased the amount of nuclear Ref-1 associated with ERp57. Moreover, ERp57 reduced by the thioredoxin-reductase/thioredoxin system stimulated the binding of AP-1 to its consensus sequence on DNA, and HeLa cells stably transfected and overexpressing ERp57 were protected against hydrogen peroxide-induced cell killing. Accordingly, ERp57 appears to cooperate with Ref-1 in the regulation of gene expression mediated by redox-sensitive transcription factors and in the adaptive response of the cell to oxidative insult.
Grillo
Caterina
C
Department of Biochemical Sciences A. Rossi Fanelli, University La Sapienza, P.le A. Moro 5, 00185 Rome, Italy.
D'Ambrosio
Chiara
C
Scaloni
Andrea
A
Maceroni
Manola
M
Merluzzi
Sonia
S
Turano
Carlo
C
Altieri
Fabio
F
D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation; D006367:HeLa Cells; D006801:Humans; D010084:Oxidation-Reduction; D019704:Protein Disulfide-Isomerases / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human