ArticleRedox biology2024
Enhancing Gpx1 palmitoylation to inhibit angiogenesis by targeting PPT1.
Article in Redox biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Protein lipidation in cardiovascular homeostasis, development, and disease.Clinical science (London, England : 1979) · 2026Review
- ProteinJournal of pharmaceutical analysis · 2026Review
- RHBDL2 drives lipid metabolic reprogramming in osteosarcoma via USP3-mediated deubiquitination of PPT1.Cell death & disease · 2026Article
- From lipid modification to cell death: the diverse roles of S-palmitoylation in cell fate decisions.Cell communication and signaling : CCS · 2026Review
- DNA Methylation-Regulated ZDHHC24 Exacerbates the Risk of Intracranial Aneurysms.Brain and behavior · 2026Article
- SREBP2-RAB11A-ZDHHC20 axis orchestrates FGFR3 palmitoylation and membrane retention to drive bladder cancer progression.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- S-palmitoylation in ferroptosis: molecular mechanisms, modulators, and interplay with autophagy.Apoptosis : an international journal on programmed cell death · 2026Review
- ZDHHC-Mediated Protein S-Palmitoylation in Cancer: Epigenetic Interfaces, Structural Logic and Therapeutic Targeting.International journal of medical sciences · 2026Review
- From EGFR PTM network to TKI resistance: spatial subtypes and targeting in lung cancer.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- Development and validation of a novel palmitoylation-related prognostic signature in head and neck squamous cell carcinoma.Translational cancer research · 2025Article
- Protein palmitoylation: A potential therapeutic target in cardiovascular diseases.Acta pharmaceutica Sinica. B · 2025Review
- Lipid overload meets S-palmitoylation: a metabolic signalling nexus driving cardiovascular and heart disease.Cell communication and signaling : CCS · 2025Review
- Recent advances in S-palmitoylation and its emerging roles in human diseases.Journal of hematology & oncology · 2025Review
- Context-dependent roles of palmitoylation in acute respiratory distress syndrome: integrating inflammation, cell death and repair.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Palmitoylation in cardiovascular diseases: Molecular mechanism and therapeutic potential.International journal of cardiology. Heart & vasculature · 2025Review
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The significance of protein S-palmitoylation in angiogenesis has been largely overlooked, leaving various aspects unexplored. Recent identification of Gpx1 as a palmitoylated protein has generated interest in exploring its potential involvement in novel pathological mechanisms related to angiogenesis. In this study, we demonstrate that Gpx1 undergoes palmitoylation at cysteine-76 and -113, with PPT1 playing a crucial role in modulating the depalmitoylation of Gpx1. Furthermore, we find that PPT1-regulated depalmitoylation negatively impacts Gpx1 protein stability. Interestingly, inhibiting Gpx1 palmitoylation, either through expression of a non-palmitoylated Gpx1 mutant or by expressing PPT1, significantly enhances neovascular angiogenesis. Conversely, in PPT1-deficient mice, angiogenesis is notably attenuated compared to wild-type mice in an Oxygen-Induced Retinopathy (OIR) model, which mimics pathological angiogenesis. Physiologically, under hypoxic conditions, Gpx1 palmitoylation levels are drastically reduced, suggesting that increasing Gpx1 palmitoylation may have beneficial effects. Indeed, enhancing Gpx1 palmitoylation by inhibiting PPT1 with DC661 effectively suppresses retinal angiogenesis in the OIR disease model. Overall, our findings highlight the pivotal role of protein palmitoylation in angiogenesis and propose a novel mechanism whereby the PPT1-Gpx1 axis modulates angiogenesis, thereby providing a potential therapeutic strategy for targeting PPT1 to combat angiogenesis.
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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.