ArticleThe Journal of clinical investigation2022
Degradation of GSPT1 causes TP53-independent cell death in leukemia while sparing normal hematopoietic stem cells.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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
40 citing papers in PubMed, 60 citations in OpenAlex.
- A scalable, high-throughput glue perturbation screening platform for molecular glue discovery.iScience · 2026Article
- Development of XYD113 as a potent and highly selective GSPT1 degrader for cancer therapy.Acta pharmacologica Sinica · 2026Article
- Non-genetic remodeling drives leukemia propagation and reveals actionable vulnerabilities in acute myeloid leukemia.Cell reports. Medicine · 2026Article
- Article
- Article
- A destination-driven framework for nanoparticle-enabled targeted protein degradation.Acta pharmaceutica Sinica. B · 2026Review
- An orally active dual CBP/p300 degrader targets core dependencies of multiple myeloma.Cell reports · 2026Article
- Synergistic targeting of eIF4A-mediated translation initiation and apoptosis in acute myeloid leukemia.Blood neoplasia · 2026Article
- Targeting "undruggable" cancer proteins: pharmacological challenges and emerging strategies.Translational cancer research · 2026Review
- Advances in molecular glue degraders for targeted protein degradation: Focus on NEK7, WEE1, CDK2, GSPT1 and VAV1.Asian journal of pharmaceutical sciences · 2026Review
- Integrated analysis of post-transcriptional regulations reveals insights into acute myeloid leukemia.Communications biology · 2025Article
- Cancer Biology of GSPT1: Mechanisms and Targeted Therapy Opportunities of Molecular Glue Degraders.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- WEE1 inhibitors synergise with mRNA translation defects via activation of the kinase GCN2.Nature communications · 2025Article
- Targeting histone H2B acetylated enhanceosomes via p300/CBP degradation in prostate cancer.Nature genetics · 2025Article
- Targeting of IRAK4 and GSPT1 enhances therapeutic efficacy in AML via c-Myc destabilization.Leukemia · 2025Article
- High cereblon expression in neuroendocrine cancer confers vulnerability to GSPT1 molecular glue degrader.Experimental hematology & oncology · 2025Article
- Myelodysplastic Neoplasms (MDS): Pathogenesis and Therapeutic Prospects.Biomolecules · 2025Review
- Nuclear Control of Mitochondrial Homeostasis and Venetoclax Efficacy in AML via COX4I1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Targeting MYC for the treatment of breast cancer: use of the novel MYC-GSPT1 degrader, GT19630.Investigational new drugs · 2025Article
- Integrated Computational Analysis Reveals Early Genetic and Epigenetic AML Susceptibility Biomarkers in Benzene-Exposed Workers.International journal of molecular sciences · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
29 authors at 7 institutions in 3 countries.
Funding
Abstract
Targeted protein degradation is a rapidly advancing and expanding therapeutic approach. Drugs that degrade GSPT1 via the CRL4CRBN ubiquitin ligase are a new class of cancer therapy in active clinical development with evidence of activity against acute myeloid leukemia in early-phase trials. However, other than activation of the integrated stress response, the downstream effects of GSPT1 degradation leading to cell death are largely undefined, and no murine models are available to study these agents. We identified the domains of GSPT1 essential for cell survival and show that GSPT1 degradation leads to impaired translation termination, activation of the integrated stress response pathway, and TP53-independent cell death. CRISPR/Cas9 screens implicated decreased translation initiation as protective following GSPT1 degradation, suggesting that cells with higher levels of translation are more susceptible to the effects of GSPT1 degradation. We defined 2 Crbn amino acids that prevent Gspt1 degradation in mice, generated a knockin mouse with alteration of these residues, and demonstrated the efficacy of GSPT1-degrading drugs in vivo with relative sparing of numbers and function of long-term hematopoietic stem cells. Our results provide a mechanistic basis for the use of GSPT1 degraders for the treatment of cancer, including TP53-mutant acute myeloid leukemia.
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.