Open AccessAn endoplasmic reticulum-specific cyclophilin.
Author(s) -
Karl W. Hasel,
James R. Glass,
Marie-Josée Godbout,
J. Gregor Sutcliffe
Publication year - 1991
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.11.7.3484
Subject(s) - cyclophilin , endoplasmic reticulum , biology , peptidylprolyl isomerase , prolyl isomerase , cyclophilin a , cis trans isomerases , cyclosporins , complementary dna , microbiology and biotechnology , cytosol , isomerase , biochemistry , gene , transplantation , pin1 , enzyme , medicine , surgery
Cyclophilin is a ubiquitously expressed cytosolic peptidyl-prolyl cis-trans isomerase that is inhibited by the immunosuppressive drug cyclosporin A. A degenerate oligonucleotide based on a conserved cyclophilin sequence was used to isolate cDNA clones representing a ubiquitously expressed mRNA from mice and humans. This mRNA encodes a novel 20-kDa protein, CPH2, that shares 64% sequence identity with cyclophilin. Bacterially expressed CPH2 binds cyclosporin A and is a cyclosporin A-inhibitable peptidyl-prolyl cis-trans isomerase. Cell fractionation of rat liver followed by Western blot (immunoblot) analysis indicated that CPH2 is not cytosolic but rather is located exclusively in the endoplasmic reticulum. These results suggest that cyclosporin A mediates its effect on cells through more than one cyclophilin and that cyclosporin A-induced misfolding of T-cell membrane proteins normally mediated by CPH2 plays a role in immunosuppression.