Disease relevance of Ppib

• We previously showed that CsA toxicity is mediated by ROS generation as well as by inhibition of peptidyl-prolyl cis-trans isomerase (PPIase) activity of CypA in CsA-treated myoblasts [FASEB J. 16 (2002) 1633] [1].
• Fractionation of differentiating murine teratocarcinoma F9 cells and extraction of the nuclear/microsomal pellets with ethidium bromide led to the purification and microsequencing of the protein mCyP-S1, a novel cyclosporin A-sensitive peptidyl-prolyl cis-trans isomerase (PPIase). mCyP-S1 is a new member of the cyclophilin class of proteins [2].

High impact information on Ppib

• First, we address whether the major cytosolic protein for CsA, cyclophilin, is directly involved in mediating the immunosuppressive activity of this drug, and, in particular, whether inhibition of this protein's peptidyl-prolyl cis-trans isomerase (PPIase) activity results in inhibition of murine T cell activation [3].
• Ab against Cyp B specifically inhibited the DNA degradation activity in the cytosol of anti-CD3-stimulated thymocytes [4].
• We purified the protein to homogeneity that induced plasmid DNA degradation from the cytosol of anti-CD3-stimulated thymocytes and found that it is identical with cyclophilin B (Cyp B), which was reported to locate in endoplasmic reticulum [4].
• Possible involvement of cyclophilin B and caspase-activated deoxyribonuclease in the induction of chromosomal DNA degradation in TCR-stimulated thymocytes [4].
• Finally, we demonstrated that TCR engagement of a murine T cell line (EL4) with anti-CD3/CD28 resulted in the release of Cyp B from the microsome fraction to the cytosol/nuclear fraction [4].

Biological context of Ppib

• Furthermore, recombinant Cyp B induced DNA degradation of naked nuclei, but did not induce internucleosomal DNA fragmentation [4].
• Our data strongly suggest that both active caspase-activated DNase and Cyp B may participate in the induction of chromosomal DNA degradation during cell death execution of TCR-stimulated thymocytes [4].
• HNF4alpha is proposed to contribute to the sex specificity of liver gene expression by positively regulating a subset of male-specific Cyp genes while concomitantly inhibiting the expression of certain female-specific Cyps and liver transcription factors, by mechanisms that are operative in male, but not female, mouse liver [5].

Anatomical context of Ppib

• Here, we show that synapsin I, a synaptic vesicle-associated protein, can be purified from Torpedo cholinergic synaptosomes through its affinity to cyclophilin B, an immunophilin that is particularly abundant in brain [6].
• Furthermore, cyclophilin B co-localizes with synapsin I in rat synaptic vesicle fractions and its levels in synaptic vesicle-containing fractions are decreased in synapsin knockout mice [6].
• The mRNAs of 58 human phase I enzymes, 26 human phase II enzymes, 23 human transporters, and five mouse Cyps were measured in the chimeric mice with humanized liver generated using hepatocytes from a Japanese donor [7].

Associations of Ppib with chemical compounds

• Synapsin associates with cyclophilin B in an ATP- and cyclosporin A-dependent manner [6].

Analytical, diagnostic and therapeutic context of Ppib

• The distribution of procollagen, Hsp47, and CyPB to the ER and/or pre-Golgi vesicles was verified by immunofluorescence [8].
• Pulse-chase experiments of cells labeled with [35S]methionine followed by immunoprecipitation during the chase period with anti-procollagen, anti-Hsp47, and anti-CyPB antibodies were performed to reveal the relationship between Hsp47/CyPB/procollagen I [8].

References