The DOI matches its Crossref record; 42 of the 46 references it cites were found in a registry or an index.
Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes
Abstract
Although the immediate receptors (immunophilins) of the immunosuppressants cyclosporin A (CsA) and FK506 are distinct, their similar mechanisms of inhibition of cell signaling suggest that their associated immunophilin complexes interact with a common target. We report here that the complexes cyclophilin-CsA and FKBP-FK506 (but not cyclophilin, FKBP, FKBP-rapamycin, or FKBP-506BD) competitively bind to and inhibit the Ca(2+)- and calmodulin-dependent phosphatase calcineurin, although the binding and inhibition of calcineurin do not require calmodulin. These results suggest that calcineurin is involved in a common step associated with T cell receptor and IgE receptor signaling pathways and that cyclophilin and FKBP mediate the actions of CsA and FK506, respectively, by forming drug-dependent complexes with and altering the activity of calcineurin-calmodulin.
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“their combined research revealed that these natural products remodeled their target proteins, a group of proteins named the immunophilins, recruiting novel interacting proteins to form entirely new ternary complexes (liu et al. 1991;Brown et al. 1994;Sabatini et al. 1994).”
From From serendipity to strategy: molecular glue degraders in cancer therapeutics (2025) · cites this paper as Liu et al. 1991
In the citing paper
“Another example of an MG is Cyclosporin A, which forms a binary complex with cyclophilin able to bind and inhibit calcineurin.80,81”
From Chasing molecular glue degraders: screening approaches (2022) · cites this paper as [80]
Citations
Cites
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Targets for Cell Cycle Arrest by the Immunosuppressant Rapamycin in Yeast
Heitman, J., Movva, N. R., & Hall, M. N. (1991) · Science · doi:10.1126/science.1715094 · Cited by 2,055
Cyclophilin: A Specific Cytosolic Binding Protein for Cyclosporin A
Handschumacher, R. E., Harding, M. W., Rice, J. S., Drugge, R. J., & Speicher, D. W. (1984) · Science · doi:10.1126/science.6238408 · Cited by 1,675
Chemistry and Biology of the Immunophilins and Their Immunosuppressive Ligands
Schreiber, S. L. (1991) · Science · doi:10.1126/science.1702904 · Cited by 1,494
Self-citationCyclophilin and peptidyl-prolyl cis-trans isomerase are probably identical proteins
Fischer, G., Wittmann‐Liebold, B., Lang, K., Kiefhaber, T., & Schmid, F. X. (1989) · Nature · doi:10.1038/337476a0 · Cited by 1,408
A receptor for the immuno-suppressant FK506 is a cis–trans peptidyl-prolyl isomerase
Harding, M. W., Gałat, A., Uehling, D., & Schreiber, S. L. (1989) · Nature · doi:10.1038/341758a0 · Cited by 1,396
Self-citationPeptidyl-prolyl cis-trans isomerase is the cyclosporin A-binding protein cyclophilin
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Research works printed but not linked: 1
- Klee, 1988, Calcineurin, Vol. 61, 149
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Takayanagi, H., Kim, S., Koga, T., Nishina, H., Isshiki, M., Yoshida, H., Saiura, A., Isobe, M., Yokochi, T., Inoue, J.-I., et al. (2002) · Developmental Cell · doi:10.1016/s1534-5807(02)00369-6 · Cited by 2,701
The mitochondrial permeability transition
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Metadata
- Authors
- Liu, J., Farmer, J. D., Lane, W. S., Friedman, J., Weissman, I., & Schreiber, S. L.
- Affiliations
- Harvard University (US)
- Howard Hughes Medical Institute (US)
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1991-08
- Volume
- 66
- Issue
- 4
- Pages
- 807-815
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1984754431
- Cited by
- 4,116
- References
- 46
- Citations by year
- 2026: 61 · 2025: 90 · 2024: 68 · 2023: 104 · 2022: 78 · 2021: 84 · 2020: 96 · 2019: 77 · 2018: 76 · 2017: 74 · 2016: 95 · 2015: 101 · 2014: 106 · 2013: 111 · 2012: 115
- FWCI
- 63.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Cancer Society
- Damon Runyon Cancer Research Foundation
- National Institutes of Health (5p01gm040660-02)
- National Cancer Institute (T32CA009302)
- National Institute of General Medical Sciences (GM-40660, GM38627)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Calpain Protease Function and Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › S100 Proteins and Annexins
- Keywords
- calcineurin, cyclophilin, cyclosporine, FKBP, FK506, immunophilins, immunosuppressants, T cell receptor signaling, IgE receptor signaling
- MeSH terms
- Amino Acid Isomerases, Amino Acid Sequence, Animals, Anti-Bacterial Agents, Base Sequence, Calmodulin, Calmodulin-Binding Proteins, Carrier Proteins, Cations, Divalent, Cloning, Molecular, Cyclosporins, Humans, Immunosuppressive Agents, Molecular Sequence Data, Molecular Weight, Oligonucleotides, Oligopeptides, Phosphoprotein Phosphatases, Polyenes, Protein Binding, Tacrolimus, Peptidylprolyl Isomerase, Calcineurin, Sirolimus, Tacrolimus Binding Proteins, Macromolecular Substances, Mice, In Vitro Techniques
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