ArticleCancer discovery2020
Posttranslational Regulation of the Exon Skipping Machinery Controls Aberrant Splicing in Leukemia.
Article in Cancer discovery, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
What it found
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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
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 100 citations in OpenAlex.
- Pooled it
- Deconvoluting the multi-faceted roles of alternative splicing events in cancer: From underlying mechanisms to innovative therapeutics.Acta pharmaceutica Sinica. B · 2026Review
- RNA splicing in health and disease.Molecular biomedicine · 2026Review
- Article
- Personalized pharmacokinetic-pharmacodynamic guided therapy via an induced pluripotent stem cell-derived multi-organoid platform in NF1-mutant breast cancer.Signal transduction and targeted therapy · 2026Article
- FBXO11 suppression rewires an NPM1-centered interactome influencing the progression of myelodysplastic syndrome.The Journal of clinical investigation · 2026Article
- Targeting SRSF6 to Enhance Cisplatin Sensitivity by Modulating Redox Balance via NFE2L1 exon 4 Splicing in ESCC.International journal of biological sciences · 2026Article
- Alternative splicing: from tumorigenesis to neoantigen-mediated cancer immunotherapy.Biomarker research · 2025Review
- USP7 mutations are associated with adverse outcomes in pediatric T cell acute lymphoblastic leukemia and lymphoma.Annals of hematology · 2025Article
- Pharmacological CLK inhibition disrupts SR protein function and RNA splicing blocking cell growth and migration in TNBC.Breast cancer research : BCR · 2025Article
- HNRNPC and m6A RNA methylation control oncogenic transcription and metabolism in T-cell leukemia.Blood · 2025Article
- Article
- Steering research on mRNA splicing in cancer towards clinical translation.Nature reviews. Cancer · 2024Review
- An Alternatively Spliced Gain-of-Function NT5C2 Isoform Contributes to Chemoresistance in Acute Lymphoblastic Leukemia.Cancer research · 2024Article
- Autoregulated splicing ofScience (New York, N.Y.) · 2024Article
- Targeting RBM39 through indisulam induced mis-splicing of mRNA to exert anti-cancer effects in T-cell acute lymphoblastic leukemia.Journal of experimental & clinical cancer research : CR · 2024Article
- Function of serine/arginine-rich splicing factors in hematopoiesis and hematopoietic malignancies.Cancer cell international · 2024Review
- SR proteins in cancer: function, regulation, and small inhibitor.Cellular & molecular biology letters · 2024Review
- Modification of BCLX pre-mRNA splicing has antitumor efficacy alone or in combination with radiotherapy in human glioblastoma cells.Cell death & disease · 2024Article
- Alternative splicing and related RNA binding proteins in human health and disease.Signal transduction and targeted therapy · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
44 authors at 10 institutions in 5 countries.
Funding
Abstract
Splicing alterations are common in diseases such as cancer, where mutations in splicing factor genes are frequently responsible for aberrant splicing. Here we present an alternative mechanism for splicing regulation in T-cell acute lymphoblastic leukemia (T-ALL) that involves posttranslational stabilization of the splicing machinery via deubiquitination. We demonstrate there are extensive exon skipping changes in disease, affecting proteasomal subunits, cell-cycle regulators, and the RNA machinery. We present that the serine/arginine-rich splicing factors (SRSF), controlling exon skipping, are critical for leukemia cell survival. The ubiquitin-specific peptidase 7 (USP7) regulates SRSF6 protein levels via active deubiquitination, and USP7 inhibition alters the exon skipping pattern and blocks T-ALL growth. The splicing inhibitor H3B-8800 affects splicing of proteasomal transcripts and proteasome activity and acts synergistically with proteasome inhibitors in inhibiting T-ALL growth. Our study provides the proof-of-principle for regulation of splicing factors via deubiquitination and suggests new therapeutic modalities in T-ALL. SIGNIFICANCE: Our study provides a new proof-of-principle for posttranslational regulation of splicing factors independently of mutations in aggressive T-cell leukemia. It further suggests a new drug combination of splicing and proteasomal inhibitors, a concept that might apply to other diseases with or without mutations affecting the splicing machinery.
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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.