The Immunochemical Distribution of Cyclophilin in Normal Mammalian Tissues

Marks, William H.; Harding, Matthew W.; Handschumacher, Robert E.; Marks, Christine; Lorber, Marc I.

doi:10.1097/00007890-199108000-00030

Cited by 38 publications

(17 citation statements)

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“…Cyclophilin 18-p53 interactions N Baum et al and nuclear localization of Cyp18 (Marks et al, 1991) and the fact that the cyclophilin inhibitor and frequently prescribed drug CsA was already shown to influence p53-mediated processes (Pyrzynska et al, 2002). Complex formation between p53 and Cyp18 was observed within subcellular extracts and between purified recombinant proteins, indicating a direct physical contact between both proteins.…”

Section: Discussionmentioning

confidence: 99%

“…Two of those, namely Cyp18 and Cyp23, belong to the cyclophilin family of PPIases. As Cyp18 was preferably found in the cytoplasm and the nucleus (Marks et al, 1991) whereas Cyp23 resides in the endoplasmic reticulum (Price et al, 1994), we focused our further analysis on potential Cyp18-p53 interactions. CoIP experiments revealed a Cyp18 association with p53 in both the cytoplasmic and nuclear fractions as shown by LC-ESI-MS/MS analysis ( Figure 1a, sections a and b).…”

Section: Physical Association Of P53 With Cyp18mentioning

confidence: 99%

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The prolyl cis/trans isomerase cyclophilin 18 interacts with the tumor suppressor p53 and modifies its functions in cell cycle regulation and apoptosis

et al. 2009

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The functional diversity of the tumor suppressor protein p53 is mainly regulated by protein interactions. In this study, we describe a new interaction with the peptidylprolyl cis/trans isomerase cyclophilin 18 (Cyp18). The interaction reduced the sequence-specific DNA binding of p53 in vitro, whereas the inhibition of the interaction increased p53-reporter gene activity in vivo. The active site of the folding helper enzyme Cyp18 was directly involved in binding. The proline-rich region (amino acids 64-91) of p53 was most likely responsible for the observed binding because a synthetic peptide comprising amino acids 68-81 of p53 inhibited this interaction, and a p53 variant containing a proline residue at position 72 (p53 P72 ) interacted with Cyp18 more effectively than the corresponding p53 R72 variant. Impairment of the Cyp18-p53 interaction induced an accumulation of cells in the G2/M phase of the cell cycle, which was more pronounced when p53 P72 was expressed compared with p53 R72 in an otherwise isogenic cellular background. Moreover, p53-dependent apoptosis was elevated in Cyp18 knockout cells, suggesting an antiapoptotic potential of Cyp18-p53 complexes. Functional in vivo data hint to a possible clinical relevance of the p53-Cyp18 interaction observed.

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Section: Discussionmentioning

confidence: 99%

Section: Physical Association Of P53 With Cyp18mentioning

confidence: 99%

The prolyl cis/trans isomerase cyclophilin 18 interacts with the tumor suppressor p53 and modifies its functions in cell cycle regulation and apoptosis

et al. 2009

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“…In 1984, CyPA was identified as the main target for the immunosuppressive drug cyclosporine A (CsA) (6,30,31,66). In humans, CyPA was found in all organs and the CyPA concentration may account for as much as 0.1-0.4% of total protein in the cell (49,59,60). CyPA was abundant in cytosolic extracts from lymphocytes and to had a high affinity for CsA (30).…”

Section: Cypa As a Molecular Chaperone With Enzymatic Propertiesmentioning

confidence: 99%

Oxidative Stress and Vascular Smooth Muscle Cell Growth: A Mechanistic Linkage by Cyclophilin A

Satoh

Nigro

Berk

2010

Antioxidants & Redox Signaling

160

111

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Inflammation and oxidative stress contribute to the pathology of many diseases, but specific therapeutic targets remain elusive. Oxidative stress, generated by excessive reactive oxygen species (ROS), promotes cardiovascular disease. However, the precise mechanism of how ROS deteriorate vascular function and promote vascular remodeling in vivo has not been clearly elucidated. Cyclophilin A (CyPA) is a 20 kD chaperone protein that is secreted from vascular smooth muscle cells (VSMC) in response to ROS, and stimulates VSMC proliferation and inflammatory cell migration in vitro and in vivo. CyPA (both intracellular and extracellular) contributes to inflammation and atherosclerosis by promoting endothelial cell (EC) apoptosis and EC expression of leukocyte adhesion molecules, stimulating leukocyte migration, enhancing T helper cell type 1 (Th1) responses, increasing proliferation of macrophages and vascular smooth muscle cells (VSMC), and increasing pro-inflammatory signal transduction in VSMC. We tested the hypothesis that CyPA contributes to cardiovascular diseases by analyzing several genetic interventions that include the CyPA knockout mouse and the CyPA overexpressing transgenic mouse (VSMC-Tg). CyPA plays a crucial role in VSMC proliferation=migration and inflammatory cell recruitment, resulting in cardiovascular diseases in vivo. Antioxid. Redox Signal. 12, 675-682.

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“…Cyclophilin A has been traditionally considered a cytoplasmic protein based on biochemical properties and its known ability to bind Cs and inhibit calcineurin, which is known to be cytoplasmic in quiescent cells. However, several previous immunolocalization studies hinted that cyclophilin A might be, at least in part, nuclear in mammalian cells (18,51,57,71). Here we show that Cpr1 is predominantly nuclear localized in yeast.…”

Section: Vol 4 2005 Cyclophilin a Is A Nuclear Regulator Of Meiosis 21mentioning

confidence: 99%

Cyclophilin A Is Localized to the Nucleus and Controls Meiosis in Saccharomyces cerevisiae

Arévalo-Rodrı́guez

Heitman²

2005

Eukaryot Cell

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Cyclophilin A is conserved from yeast to humans and mediates the ability of cyclosporine to perturb signal transduction cascades via inhibition of calcineurin. Cyclophilin A also catalyzes cis-trans peptidyl-prolyl isomerization during protein folding or conformational changes; however, cyclophilin A is not essential in yeast or human cells, and the true biological functions of this highly conserved enzyme have remained enigmatic. In Saccharomyces cerevisiae, cyclophilin A becomes essential in cells compromised for the nuclear prolyl-isomerase Ess1, and cyclophilin A physically interacts with two nuclear histone deacetylase complexes, Sin3-Rpd3 and Set3C, which both control meiosis. Here we show that cyclophilin A is localized to the nucleus in yeast cells and governs the meiotic gene program to promote efficient sporulation. The prolyl-isomerase activity of cyclophilin A is required for this meiotic function. We document that cyclophilin A physically associates with the Set3C histone deacetylase and analyze in detail the structure of this protein-protein complex. Genetic studies support a model in which cyclophilin A controls meiosis via Set3C and an additional target. Our findings reveal a novel nuclear role for cyclophilin A in governing the transcriptional program required for the vegetative to meiotic developmental switch in budding yeast.Cyclophilin A was originally identified as the intracellular receptor of the immunosuppressive drug cyclosporine (Cs), and the two molecules form a complex that binds to and inhibits the protein phosphatase calcineurin, preventing T-cell activation in mammals (36,52,53). Although cyclophilin A is highly conserved from yeast to humans, establishing the normal biological functions of this nonessential protein has proven elusive. Cyclophilin A is the founding member of a class of ubiquitous and highly conserved enzymes collectively known as peptidyl-prolyl cis-trans isomerases, or prolyl-isomerases, which catalyze cis-trans isomerization of the peptide bonds preceding proline residues. The prolyl-isomerase group spans three structurally unrelated protein families: the cyclophilins, FKBPs (for FK506 binding proteins), and parvulins (34,40,69,81). All three families are present in the budding yeast Saccharomyces cerevisiae, which expresses eight different cyclophilins (Cpr1 to Cpr8), four FKBPs (Fpr1 to Fpr4), and a single parvulin (Ess1), which is the only essential prolyl-isomerase in this organism (20,37,39). Cellular roles have been established for several prolylisomerases in both mammals and yeast. In mammals, cyclophilin A associates with the human immunodeficiency virus type 1 Gag polyprotein and is incorporated into virion particles, where it is required for human immunodeficiency virus type 1 infectivity (7,9,28,84). Cyclophilin A also binds to and regulates the tyrosine kinase Itk in T lymphocytes (11,55). FKBP12regulates the activity of the ryanodine receptor, a calcium release channel in the sarcoplasmic reticulum (61,85,86), and both FKBP12 and cyclophilin A intera...

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The Immunochemical Distribution of Cyclophilin in Normal Mammalian Tissues

Cited by 38 publications

References 0 publications

The prolyl cis/trans isomerase cyclophilin 18 interacts with the tumor suppressor p53 and modifies its functions in cell cycle regulation and apoptosis

The prolyl cis/trans isomerase cyclophilin 18 interacts with the tumor suppressor p53 and modifies its functions in cell cycle regulation and apoptosis

Oxidative Stress and Vascular Smooth Muscle Cell Growth: A Mechanistic Linkage by Cyclophilin A

Cyclophilin A Is Localized to the Nucleus and Controls Meiosis in Saccharomyces cerevisiae

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