The helix-loop-helix/leucine repeat transcription factor USF can be functionally regulated in a redox-dependent manner.
We showed previously that the DNA-binding capacity of the helix-loop-helix/leucine repeat transcription factor USF43 is lowered dramatically under nonreducing conditions. This report defines the molecular basis of this effect by showing (i) that the only two USF43 cysteine residues, both present within the helix-loop-helix protein-protein interface domain, are required for this regulation, (ii) that the sulfhydryl groups of these cysteine residues are the actual targets of this regulation, (iii) that oxidation of these groups results in both intra- and intermolecular nonrandom covalent links, (iv) that this redox modulation of USF43 DNA-binding potential can translate in vitro into a specific modulation of its ability to activate transcription from a USF-responsive promoter. The implications of these modulations of USF43 function in response to redox changes are discussed with regard to the apparent paradox of USF strong activation potential and its ubiquitous distribution in all cell types tested.
Pognonec
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Rockefeller University, New York, New York 10021-6399.
Kato
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Roeder
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D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D003545:Cysteine; D004268:DNA-Binding Proteins / Q000378:metabolism*; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides; D010084:Oxidation-Reduction; D011401:Promoter Regions, Genetic; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D015183:Restriction Mapping; D012694:Serine; D014157:Transcription Factors / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D014158:Transcription, Genetic; D051720:Upstream Stimulatory Factors
D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; D014157:Transcription Factors; D051720:Upstream Stimulatory Factors; D012694:Serine; D003545:Cysteine