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 cisltrans 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.
Krummrei
U
U
Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg, Germany.
Bang
R
R
Schmidtchen
R
R
Brune
K
K
Bang
H
H
D000591:Amino Acid Isomerases / Q000032:analysis / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D021983:Cyclophilins; D016572:Cyclosporine / Q000378:metabolism; D003600:Cytosol / Q000737:chemistry; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D008264:Macrophages / Q000737:chemistry*; D051379:Mice; D008969:Molecular Sequence Data; D019696:Peptidylprolyl Isomerase; D011994:Recombinant Proteins / Q000378:metabolism; D015032:Zinc / Q000378:metabolism* / Q000494:pharmacology
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D011994:Recombinant Proteins; C081786:cyclophilin B; D016572:Cyclosporine; D004247:DNA; D000591:Amino Acid Isomerases; D021983:Cyclophilins; D019696:Peptidylprolyl Isomerase; D015032:Zinc