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-Spl. Moreover, DNA binding of apo-Sp1, but not of the hole-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 Spl. (C) 1994 Academic Press Inc.