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

The association of cyclosporin A (CsA) immunosuppression with inhibiti on of transcription factor-dependent lymphokine gene activation formed the basis of our decision to investigate nuclear-associated Cyp isofo rms. Immunofluorescence microscopy of mouse macrophages cell line with a monoclonal antibody mAb7F1 raised against CypA shows a co-localisat ion of CypA in the nucleus and in the cytosol, Nuclear CypA binds to D NA in a zinc ion-dependent manner, in contrast to recombinant CypB. Pe ptidyl-prolyl cis/trans isomerase (PPIase) activity of nuclear CypA is inhibited by zinc ions, The zinc inhibited CypA does not bind cyclosp orin A (CsA). We suggest that nuclear Cyp in complex with zinc ions re cognizes DNA sequences and is involved in transcription modulating pro cesses.