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Cooperation of protein disulfide isomerase and redox environment in the regulation of NF‐κB and AP1 binding to DNA
Author(s) -
Clive Diana R.,
Greene James J.
Publication year - 1996
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.638
Subject(s) - protein disulfide isomerase , ap 1 transcription factor , biochemistry , transcription factor , chemistry , electrophoretic mobility shift assay , glutathione , dna , redox , glutaredoxin , dna binding protein , binding site , plasma protein binding , enzyme , gene , organic chemistry
Most transcription factors are multimeric complexes whose subunits depend on strict conformational requirements to form the active unit. Among these requirements is the presence of appropriate sulfhydryl interactions that are critical to transcription factor binding to cognate DNA recognition sites. Our experiments now suggest that modulation of these sulfhydryls may involve the action of thiol‐modifying oxido‐reductases such as protein disulfide isomerase (PDI). Electrophoretic mobility shift titration experiments incorporating different ratios of GSH:GSSG indicated that changes in GSH and GSSG concentrations corresponding to redox potential differences of as little as ±15 mV enabled or abolished binding of NF‐κB and AP1 to their cognate DNA sites. Moreover, this binding range was modulated significantly by the addition of purified protein disulfide isomerase (PDI). Collectively, these results suggest that a reversible oxidation/reduction signalling pathway may exist in the cell whereby localized changes in redox potentials and/or oxido‐reductase activity can be functionally relevant in the regulation of critical gene expression events.