ArticleNature2015
Theileria parasites secrete a prolyl isomerase to maintain host leukocyte transformation.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 137 citations in OpenAlex.
- Epigenetic silencing of innate and adaptive immunity genes underlies the immune evasion cancer hallmark in Theileria-infected B-cells.PLoS pathogens · 2026Article
- Epigenetic landscape of the H3K27me3 mark in macrophages transformed by Theileria annulata.Communications biology · 2026Article
- Acute infection with the U.S. isolate ofFrontiers in veterinary science · 2026Article
- Integrative molecular and serum proteomic insights into subclinicalCurrent research in parasitology & vector-borne diseases · 2026Article
- Genomic characterization of host gene alterations in Theileria annulata-transformed leukocytes.Communications biology · 2025Article
- The Culture Technology for the Transforming Parasite-Theileria Annulata Schizont-Infected Cells: Past-Present-Perspective.Acta parasitologica · 2025Review
- Identification of genetic variations linked to buparvaquone resistance in Theileria annulata infecting dairy cattle in India.PloS one · 2025Article
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- Pin1-catalyzed conformational regulation after phosphorylation: A distinct checkpoint in cell signaling and drug discovery.Science signaling · 2024Review
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- Review
- Theileria parasites sequester host eIF5A to escape elimination by host-mediated autophagy.Nature communications · 2024Article
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- The role of the master cancer regulator Pin1 in the development and treatment of cancer.Frontiers in cell and developmental biology · 2024Review
- Dual RNA-seq to catalogue host and parasite gene expression changes associated with virulence of T. annulata-transformed bovine leukocytes: towards identification of attenuation biomarkers.Scientific reports · 2023Article
- Cancerogenic parasites in veterinary medicine: a narrative literature review.Infectious agents and cancer · 2023Review
- Identification of a Novel Interaction betweenMicrobiology spectrum · 2023Article
- Multiplex ddPCR: A Promising Diagnostic Assay for Early Detection and Drug Monitoring in Bovine Theileriosis.Pathogens (Basel, Switzerland) · 2023Article
- Activation of telomerase activity and telomere elongation of host cells byFrontiers in microbiology · 2023Article
- Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on byCommentary:2018
Authors and funding
14 authors at 10 institutions in 3 countries.
Funding
Abstract
Infectious agents develop intricate mechanisms to interact with host cell pathways and hijack their genetic and epigenetic machinery to change host cell phenotypic states. Among the Apicomplexa phylum of obligate intracellular parasites, which cause veterinary and human diseases, Theileria is the only genus that transforms its mammalian host cells. Theileria infection of bovine leukocytes induces proliferative and invasive phenotypes associated with activated signalling pathways, notably JNK and AP-1 (ref. 2). The transformed phenotypes are reversed by treatment with the theilericidal drug buparvaquone. We used comparative genomics to identify a homologue of the peptidyl-prolyl isomerase PIN1 in T. annulata (TaPIN1) that is secreted into the host cell and modulates oncogenic signalling pathways. Here we show that TaPIN1 is a bona fide prolyl isomerase and that it interacts with the host ubiquitin ligase FBW7, leading to its degradation and subsequent stabilization of c-JUN, which promotes transformation. We performed in vitro and in silico analysis and in vivo zebrafish xenograft experiments to demonstrate that TaPIN1 is directly inhibited by the anti-parasite drug buparvaquone (and other known PIN1 inhibitors) and is mutated in a drug-resistant strain. Prolyl isomerization is thus a conserved mechanism that is important in cancer and is used by Theileria parasites to manipulate host oncogenic signalling.
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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 OpenQuestion graph.