The DNA binding activity and the dimerization ability of the thyroid transcription factor I are redox regulated.
The DNA binding activity of the thyroid transcription factor-1 (TTF-1), a homeodomain-containing protein implicated in the control of thyroid- and lung-specific transcription, is controlled, in vitro, by the redox potential. Oxidation decreases TTF-1 DNA binding activity, which is fully restored upon exposure to reducing agents. The decrease in DNA binding activity is due to the formation of disulfide bond(s), formed between two specific cysteine residues located outside the TTF-1 homeodomain; hence, oxidation does not appear to directly hinder TTF-1/DNA contacts. Disulfide bond formation seems to stabilize preexisting, loosely associated, TTF-1 dimers, which, upon oxidation, proceed in the formation of specific, higher order oligomers.
Arnone
M I
MI
Stazione Zoologica A. Dohrn, Villa Comunale, Napoli, Italy.
Zannini
M
M
Di Lauro
R
R
D000478:Alkylation; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D016384:Consensus Sequence; D003545:Cysteine / Q000378:metabolism; D003553:Cystine / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D003958:Diamide / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D006367:HeLa Cells; D018398:Homeodomain Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D011401:Promoter Regions, Genetic; D011487:Protein Conformation / Q000187:drug effects; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D013964:Thyroid Neoplasms / Q000473:pathology; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D011993:Recombinant Fusion Proteins; D003958:Diamide; D003553:Cystine; D004247:DNA; D005978:Glutathione; D003545:Cysteine; D004229:Dithiothreitol