ArticleClinical pharmacology and therapeutics2018
TSPYL Family Regulates CYP17A1 and CYP3A4 Expression: Potential Mechanism Contributing to Abiraterone Response in Metastatic Castration-Resistant Prostate Cancer.
Article in Clinical pharmacology and therapeutics, 2018. 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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Who cites it
26 citing papers in PubMed, 40 citations in OpenAlex.
- TSPY-like 2, Beyond the Histone Chaperone Role.Biomolecules · 2026Review
- Evaluating the prognosis of prostate cancer through metabolic pathways.Discover oncology · 2025Article
- Nodularin-R Synergistically Enhances Abiraterone Against Castrate- Resistant Prostate Cancer via PPP1CA Inhibition.Journal of cellular and molecular medicine · 2024Article
- Integrated immunogenomic analyses of single-cell and bulk profiling construct a T cell-related signature for predicting prognosis and treatment response in osteosarcoma.Discover oncology · 2024Article
- Prostate Cancer: A Review of Genetics, Current Biomarkers and Personalised Treatments.Cancer reports (Hoboken, N.J.) · 2024Review
- Predictive model of castration resistance in advanced prostate cancer by machine learning using genetic and clinical data: KYUCOG-1401-A study.BJC reports · 2024Article
- TSPYL1 as a Critical Regulator of TGFβ Signaling through Repression of TGFBR1 and TSPYL2.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The effect of genetic variants in the transcription factor TSPYL family on the CYP3A4 mediated cyclosporine metabolism in kidney transplant patients.Clinical and translational science · 2024Article
- Insights into the Cellular Localization and Functional Properties of TSPYL5 Protein.International journal of molecular sciences · 2023Article
- Minor intron splicing is critical for survival of lethal prostate cancer.Molecular cell · 2023Article
- AhR and Wnt/β-Catenin Signaling Pathways and Their Interplay.Current issues in molecular biology · 2023Review
- Genetic variations predicting progression with docetaxel and novel androgen-receptor pathway inhibitors.Cancer science · 2023Article
- Sex differences in the intergenerational link between maternal and neonatal whole blood DNA methylation: a genome-wide analysis in 2 birth cohorts.Clinical epigenetics · 2023Article
- Cytochrome P450 Transcriptional Regulation by Testis-Specific Y-Encoded-Like Protein: Identification of Novel Upstream Transcription Factors.Drug metabolism and disposition: the biological fate of chemicals · 2023Article
- Ginsenoside Rg3 increases gemcitabine sensitivity of pancreatic adenocarcinoma via reducing ZFP91 mediated TSPYL2 destabilization.Journal of ginseng research · 2022Article
- Selective Serotonin Reuptake Inhibitor Pharmacokinetics During Pregnancy: Clinical and Research Implications.Frontiers in pharmacology · 2022Article
- Testis- specific Y-encoded- like protein 1 and cholesterol metabolism: Regulation ofFrontiers in pharmacology · 2022Article
- Why We Need to Take a Closer Look at Genetic Contributions to CYP3A Activity.Frontiers in pharmacology · 2022Review
- Article
- Genetic Polymorphisms and Pharmacotherapy for Prostate Cancer.JMA journal · 2021Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
The testis-specific Y-encoded-like protein (TSPYL) gene family includes TSPYL1 to TSPYL6. We previously reported that TSPYL5 regulates cytochrome P450 (CYP) 19A1 expression. Here we show that TSPYLs, especially TSPYL 1, 2, and 4, can regulate the expression of many CYP genes, including CYP17A1, a key enzyme in androgen biosynthesis, and CYP3A4, an enzyme that catalyzes the metabolism of abiraterone, a CYP17 inhibitor. Furthermore, a common TSPYL1 single nucleotide polymorphism (SNP), rs3828743 (G/A) (Pro62Ser), abolishes TSPYL1's ability to suppress CYP3A4 expression, resulting in reduced abiraterone concentrations and increased cell proliferation. Data from a prospective clinical trial of 87 metastatic castration-resistant prostate cancer patients treated with abiraterone acetate/prednisone showed that the variant SNP genotype (A) was significantly associated with worse response and progression-free survival. In summary, TSPYL genes are novel CYP gene transcription regulators, and genetic alteration within these genes significantly influences response to drug therapy through transcriptional regulation of CYP450 genes.
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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.