CYCLOPHILIN-A IS A ZINC-DEPENDENT DNA-BINDING PROTEIN IN MACROPHAGES

The association of cyclosporin A (CsA) immunosuppression with inhibition of transcription factor-dependent lymphokine gene activation formed the basis of our decision to investigate nuclear-associated Cyp isoforms. Immunofluorescence microscopy of mouse macrophages cell line with a monoclonal antibody mAb7F1 raised against CypA shows a co-localisation of CypA in the nucleus and in the cytosol, Nuclear CypA binds to DNA in a zinc ion-dependent manner, in contrast to recombinant CypB. Peptidyl-prolyl cis/trans isomerase (PPIase) activity of nuclear CypA is inhibited by zinc ions, The zinc inhibited CypA does not bind cyclosporin A (CsA). We suggest that nuclear Cyp in complex with zinc ions recognizes DNA sequences and is involved in transcription modulating processes.