Peptidyl-prolyl cis-trans isomerase C (Cyclophilin C) (PPIC)

Peptidyl-prolyl cis-trans isomerase C (PPIC), commonly known as Cyclophilin C, is a member of the immunophilin family of proteins characterized by their ability to catalyze the cis-trans isomerization of proline imidic peptide bonds [1.4.1, 1.4.2]. This enzymatic activity is a critical rate-limiting step in the folding and maturation of various proteins within the cell [1.3.1, 1.4.2]. PPIC is localized to the cytoplasm and the endoplasmic reticulum, and it can also be secreted into the extracellular space where it acts as a pro-inflammatory mediator [1.2.1, 1.3.4]. It is a well-known target of the immunosuppressive drug cyclosporine A, which forms a complex with PPIC to inhibit the phosphatase calcineurin, thereby blocking T-cell activation and the immune response [1.1.1, 1.4.2]. Beyond its role in immunity, PPIC is involved in the replication cycles of several viruses, including hepatitis C and HIV-1, by serving as a host chaperone for viral proteins [1.2.3, 1.3.1]. It has also been implicated in the pathogenesis of cardiovascular diseases, cancer, and inflammation, with elevated serum levels serving as potential biomarkers for coronary artery disease [1.2.1, 1.3.2]. Consequently, PPIC and other cyclophilins are significant therapeutic targets for the development of both immunosuppressive and non-immunosuppressive inhibitors aimed at treating viral infections, inflammatory conditions, and fibrotic diseases [1.1.2, 1.2.2].

Other names

Cyclophilin CPPIase CRotamase CCYPC

Inhibition of peptidyl-prolyl cis-trans isomerase activity and formation of a drug-target complex that inhibits calcineurin phosphatase activity [1.1.1, 1.4.2].