Characterization of the DNA-binding properties of the early growth response-1 (Egr-1) transcription factor: evidence for modulation by a redox mechanism.
The binding of the transcription factor early growth response-1 (Egr-1) to its specific DNA-binding sequence GCGGGGGCG occurs through the interaction of three zinc finger motifs. DNA binding by Egr-1 can be modified by alteration of reduction-oxidation (redox) state. Using gel retardation assays, we show that binding of Egr-1 protein is specific and is dependent on the presence of reducing agents in a dose-dependent manner. The zinc finger region is the domain subject to conformation changes by redox. Oxidized or metal-free Egr-1 does not bind. Nuclear extracts of several cell types contain a heat-sensitive factor(s) that induces the ability of Egr-1 protein to bind to DNA in otherwise suboptimal conditions containing insufficient reducing agent. This inducing activity may be replaced by Ref-1, a protein identified and characterized by Curran and co-workers (Xanthoudakis and Curran, 1992). The possibility arises that the transcription-regulating activity of Egr-1 may be regulated by the redox state in the cell via factors such as Ref-1 that modulate its DNA-binding activity.
Huang
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La Jolla Cancer Research Foundation, CA 92037.
Adamson
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D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002467:Cell Nucleus / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D051766:Early Growth Response Protein 1; D006367:HeLa Cells; D006801:Humans; D017874:Immediate-Early Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000502:physiology; D010084:Oxidation-Reduction; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; C058452:HAP1 protein, S cerevisiae; D017874:Immediate-Early Proteins; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors