ArticleNature chemical biology2016
Cyclophilin A promotes cell migration via the Abl-Crk signaling pathway.
Article in Nature chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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The trial behind it
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Who cites it
26 citing papers in PubMed.
- ABL kinases regulate FGF signaling independent of CRK phosphorylation to prevent Peters anomaly type II.Nature communications · 2026Article
- CypA Mediates Non-Small Cell Lung Cancer Chemoresistance by Attenuating Ferroptosis via Stabilizing SLC7A11.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Molecular regulation by ubiquitin-specific proteases (USPs) in HCC: cell cycle, oncogenic signaling, and beyond.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Differential Expression of Neurodegeneration-Related Genes in SH-SY5Y Neuroblastoma Cells Under the Influence of Cyclophilin A: Could the Enzyme be a Likely Trigger and Therapeutic Target for Alzheimer's Disease?Neurochemical research · 2024Article
- PPIA dictates NRF2 stability to promote lung cancer progression.Nature communications · 2024Article
- Inhibitors of Cyclophilin A: Current and Anticipated Pharmaceutical Agents for Inflammatory Diseases and Cancers.Molecules (Basel, Switzerland) · 2024Review
- Crosstalk between integrin/FAK and Crk/Vps25 governs invasion of bovine mammary epithelial cells byiScience · 2023Article
- Review
- Application of small extracellular vesicles in the diagnosis and prognosis of nasopharyngeal carcinoma.Frontiers in cell and developmental biology · 2023Review
- Imatinib can act as an Allosteric Activator of Abl Kinase.Journal of molecular biology · 2022Article
- Purification and characterization of Cyclophilin: a protein associated with protein folding in Salmonella Typhimurium.Archives of microbiology · 2021Article
- [Expression of cyclophilin A in oral squamous cell carcinoma and its effect on cell proliferation and invasion].Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2021Article
- Cyclophilin A: a key player for etiological agent infection.Applied microbiology and biotechnology · 2021Review
- Cyclophilin A Inhibitor Debio-025 Targets Crk, Reduces Metastasis, and Induces Tumor Immunogenicity in Breast Cancer.Molecular cancer research : MCR · 2020Article
- MiR-194-5p inhibited metastasis and EMT of nephroblastoma cells through targeting Crk.The Kaohsiung journal of medical sciences · 2020Article
- Cyclophilin A allows the allosteric regulation of a structural motif in the disordered domain 2 of NS5A and thereby fine-tunes HCV RNA replication.The Journal of biological chemistry · 2019Article
- PEAK3/C19orf35 pseudokinase, a new NFK3 kinase family member, inhibits CrkII through dimerization.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Exosomal cyclophilin A as a novel noninvasive biomarker for Epstein-Barr virus associated nasopharyngeal carcinoma.Cancer medicine · 2019Article
- Structural basis of interaction between dimeric cyclophilin 1 and Myb1 transcription factor in Trichomonas vaginalis.Scientific reports · 2018Article
- Ubiquitin-specific protease 4 promotes hepatocellular carcinoma progression via cyclophilin A stabilization and deubiquitination.Cell death & disease · 2018Article
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Authors and funding
10 authors.
Funding
Abstract
Cyclophilin A (CypA) is overexpressed in a number of human cancer types, but the mechanisms by which the protein promotes oncogenic properties of cells are not understood. Here we demonstrate that CypA binds the CrkII adaptor protein and prevents it from switching to the inhibited state. CrkII influences cell motility and invasion by mediating signaling through its SH2 and SH3 domains. CrkII Tyr221 phosphorylation by the Abl or EGFR kinases induces an inhibited state of CrkII by means of an intramolecular SH2-pTyr221 interaction, causing signaling interruption. We show that the CrkII phosphorylation site constitutes a binding site for CypA. Recruitment of CypA sterically restricts the accessibility of Tyr221 to kinases, thereby suppressing CrkII phosphorylation and promoting the active state. Structural, biophysical and in vivo data show that CypA augments CrkII-mediated signaling. A strong stimulation of cell migration is observed in cancer cells wherein both CypA and CrkII are greatly upregulated.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.