Role of zinc-coordination and of the glutathione redox couple in the redox susceptibility of human transcription factor Sp1.
We show that thiol-groups confer redox-susceptibility to the zinc-finger transcription factor Sp1 and that this redox-susceptibility is prevented by DNA-binding and depends on zinc-coordination of the protein. Apo-Sp1 contained in metal depleted nuclear extracts of human K562 cells exhibited a markedly increased susceptibility towards oxidizing and alkylating agents, as compared to holo-Sp 1. Moreover, DNA binding of apo-Sp1, but not of the holo-protein, was dramatically decreased in the presence of GSH/GSSG ratios within the physiological range. We compared these results with the redox behaviour of two other transcription factors, OTF-1 and NF1, which was found to be different in several aspects from that of Sp1.
Knoepfel
L
L
Department of Biology, University of Rome, Tor Vergata, Rome, Italy.
Steinkühler
C
C
Carrì
M T
MT
Rotilio
G
G
D001059:Apoproteins / Q000378:metabolism; D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D005033:Ethylmaleimide / Q000494:pharmacology; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism*; D019803:Glutathione Disulfide; D006801:Humans; D007700:Kinetics; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010084:Oxidation-Reduction; D016329:Sp1 Transcription Factor / Q000737:chemistry / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D015032:Zinc / Q000378:metabolism*
D001059:Apoproteins; D009838:Oligodeoxyribonucleotides; D016329:Sp1 Transcription Factor; D005978:Glutathione; D015032:Zinc; D005033:Ethylmaleimide; D019803:Glutathione Disulfide