ArticleThe Biochemical journal2015
Identification of amino acid determinants in CYP4B1 for optimal catalytic processing of 4-ipomeanol.
Article in The Biochemical journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- The Emerging World of TCR-T Cell Trials Against Cancer: A Systematic Review.Technology in cancer research & treatment · 2019Pooled it
- CYP4B1 Expression in Breast Cancer: An Immunohistochemical Study with Complementary in silico Analyses.Breast cancer (Dove Medical Press) · 2026Article
- Genomic signatures of selection in drug metabolizing genes across cattle populations.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Article
- Reclassification of ATM Missense Variants of Uncertain Significance by Integrating Results from Systematic Functional Assays into an ACMG Points-Based Framework.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Functional analysis of CYP4B1 enzymes from apes and humans uncovers evolutionary hot spots for adaptations of the catalytical function.PLoS genetics · 2025Article
- CYP4B1 inhibits lung adenocarcinoma progression via PI3K/AKT/mTOR pathway: mechanistic insights and development of a CYP4B1-related prognostic signature.Frontiers in oncology · 2025Article
- Preliminary proteomic analysis of mouse lung tissue treated with cyclophosphamide and Venetin-1.Scientific reports · 2024Article
- A MYCN-driven de-differentiation profile identifies a subgroup of aggressive retinoblastoma.Communications biology · 2024Article
- Designing cytochrome P450 enzymes for use in cancer gene therapy.Frontiers in bioengineering and biotechnology · 2024Review
- CYP4B1 polymorphisms and the risk of breast cancer in Chinese women: a case-control study.BMC cancer · 2023Article
- Regulation of early diagnosis and prognostic markers of lung adenocarcinoma in immunity and hypoxia.Scientific reports · 2023Article
- Spotlight on CYP4B1.International journal of molecular sciences · 2023Review
- Optimized NGFR-derived hinges for rapid and efficient enrichment and detection of CAR T cellsMolecular therapy oncolytics · 2022Article
- Proteomic and transcriptomic profiles of human urothelial cancer cells with histone deacetylase 5 overexpression.Scientific data · 2022Article
- Single-cell RNA sequencing analysis to explore immune cell heterogeneity and novel biomarkers for the prognosis of lung adenocarcinoma.Frontiers in genetics · 2022Article
- Genetic Engineering and Enrichment of Human NK Cells for CAR-Enhanced Immunotherapy of Hematological Malignancies.Frontiers in immunology · 2022Article
- A novel CD34-derived hinge for rapid and efficient detection and enrichment of CAR T cells.Molecular therapy oncolytics · 2021Article
- Epigenetic Priming of Bladder Cancer Cells With Decitabine Increases Cytotoxicity of Human EGFR and CD44v6 CAR Engineered T-Cells.Frontiers in immunology · 2021Article
- CYP4B1 is a prognostic biomarker and potential therapeutic target in lung adenocarcinoma.PloS one · 2021Article
- Heterologous Expression and Functional Characterization of Novel CYP2C9 Variants Identified in the Alaska Native People.The Journal of pharmacology and experimental therapeutics · 2020Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Mammalian CYP4B1 enzymes are cytochrome P450 mono-oxygenases that are responsible for the bioactivation of several exogenous pro-toxins including 4-ipomeanol (4-IPO). In contrast with the orthologous rabbit enzyme, we show here that native human CYP4B1 with a serine residue at position 427 is unable to bioactivate 4-IPO and does not cause cytotoxicity in HepG2 cells and primary human T-cells that overexpress these enzymes. We also demonstrate that a proline residue in the meander region at position 427 in human CYP4B1 and 422 in rabbit CYP4B1 is important for protein stability and rescues the 4-IPO bioactivation of the human enzyme, but is not essential for the catalytic activity of the rabbit CYP4B1 protein. Systematic substitution of native and p.S427P human CYP4B1 with peptide regions from the highly active rabbit enzyme reveals that 18 amino acids in the wild-type rabbit CYP4B1 protein are key for conferring high 4-IPO metabolizing activity. Introduction of 12 of the 18 amino acids that are also present at corresponding positions in other human CYP4 family members into the p.S427P human CYP4B1 protein results in a mutant human enzyme (P+12) that is as stable and as active as the rabbit wild-type CYP4B1 protein. These 12 mutations cluster in the predicted B-C loop through F-helix regions and reveal new amino acid regions important to P450 enzyme stability. Finally, by minimally re-engineering the human CYP4B1 enzyme for efficient activation of 4-IPO, we have developed a novel human suicide gene system that is a candidate for adoptive cellular therapies in humans.
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