ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
USP5 Promotes Ripretinib Resistance in Gastrointestinal Stromal Tumors by MDH2 Deubiquition.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed.
- The role of protein palmitoylation in disease pathogenesis and therapeutic innovation.Annals of medicine · 2026Review
- Crosstalk between ubiquitination and other post-translational modifications in cardiovascular diseases.iScience · 2026Review
- Exploring the functional role of palmitoylation genes in clear cell renal cell carcinoma and their impact on tumor microenvironment.BMC genomic data · 2026Article
- PRMT3-Mediated Arginine Methylation Stabilizes PCSK9 to Promote Aortic Valve Calcification.Circulation · 2026Article
- USP5 in cancer: a therapeutic window into metabolism and drug resistance.Journal of translational medicine · 2026Review
- USP5-mediated CD73 deubiquitination drives osimertinib resistance via PI3K/AKT and glycolysis activation in LUAD.iScience · 2026Article
- Decoding the PTM code of cGAS-STING in gastric cancer: from innate DNA sensing to precision combination therapy.Frontiers in immunology · 2026Review
- Multi-omics and experimental validation identify USP54 as a prognostic deubiquitinase promoting pancreatic ductal adenocarcinoma progression within the immune microenvironment.Frontiers in immunology · 2026Article
- USP10 stabilizes FOXM1 through KAT5-mediated acetylation to suppress cell senescence and promote melanoma malignant progression.International journal of biological sciences · 2026Article
- LC3-dependent intercellular transfer of phosphorylated STAT1/2 elicits CXCL9+ macrophages and enhances radiation-induced antitumor immunity.The Journal of clinical investigation · 2025Article
- Malate targets pyruvate kinase M2 to promote colorectal cancer cell cycle arrest and tumor suppression.Molecular biomedicine · 2025Article
- Recent advances in S-palmitoylation and its emerging roles in human diseases.Journal of hematology & oncology · 2025Review
- Role of S-palmitoylation in digestive system diseases.Cell death discovery · 2025Review
- Palmitoylation in cardiovascular diseases: Molecular mechanism and therapeutic potential.International journal of cardiology. Heart & vasculature · 2025Review
- The role of protein S-acylation in vascular injury associated with metabolic disorders.Frontiers in endocrinology · 2025Review
- The effect of ubiquitination and deubiquitination to imatinib resistance in gastrointestinal stromal tumors.Frontiers in oncology · 2025Review
- Deubiquitylase USP52 Promotes Bladder Cancer Progression by Modulating Ferroptosis through Stabilizing SLC7A11/xCT.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- USP5 Promotes Ripretinib Resistance in Gastrointestinal Stromal Tumors by MDH2 Deubiquition.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors.
Funding
Abstract
Ripretinib, a broad-spectrum inhibitor of the KIT and PDGFRA receptor tyrosine kinases, is designated as a fourth-line treatment for gastrointestinal stromal tumor (GIST). It is tailored for patients resistant to imatinib, sunitinib, and regorafenib. As its increasing use, instances of resistance to ripretinib are becoming more frequent. Unfortunately, there are currently no scientifically mature treatment options available for patients resistant to ripretinib. Posttranslational modifications (PTMs) such as ubiquitination, in conjunction with its interplay with other modifications, play a collective role in regulating tumor initiation and progression. However, the specific association between ubiquitination and ripretinib resistance is not reported. Through proteome-ubiquitinome sequencing, increased levels of the USP5 protein and decreased ubiquitination in ripretinib-resistant GISTs are detected. Subsequent examination of the mass spectrometry findings validated the interaction through which TRIM21 governs USP5 expression via ubiquitination, and USP5 regulates MDH2 expression through deubiquitination, consequently fostering ripretinib resistance in GIST. Moreover, ZDHHC18 can palmitoylate MDH2, preventing its ubiquitination and further increasing its protein stability. The research underscores the correlation between posttranslational modifications, specifically ubiquitination, and drug resistance, emphasizing the potential of targeting the USP5-MDH2 axis to counteract ripretinib resistance in GIST.
Indexed as
Identifiers
What OpenQuestion holds
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.