ArticleScience translational medicine2021
Ubiquitination and degradation of SUMO1 by small-molecule degraders extends survival of mice with patient-derived tumors.
Article in Science translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Chrysosplenetin-induced TMED3 aggregation triggers unfolded protein response in pancreatic cancer.EMBO molecular medicine · 2026Article
- Molecular Glue Degraders Enhance CAPRIN1-Dependent Lysosomal Degradation of APP and Reduce Amyloid β in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Itgb1-Mediated Stabilization of Vimentin Alleviates Excessive Mechanical Stress-Induced Nucleus Pulposus Cell Pyroptosis and Intervertebral Disc Degeneration via PINK1-Parkin-Dependent Mitophagy.Cell proliferation · 2026Article
- Targeted Degradation of eEF2K by a Structure-Guided PROTAC Strategy for the Treatment of Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Exploring Novel E3 Ligases and Neosubstrates for Molecular Glue Degraders and Therapeutic Applications in Cancer.Oncology research · 2026Review
- FBXO42 promotes hepatocellular carcinoma progression via mediating p57Kip2 ubiquitination and degradation.European journal of medical research · 2025Article
- The impact of dysregulation SUMOylation on prostate cancer.Journal of translational medicine · 2025Review
- Old players and new insights: unraveling the role of RNA-binding proteins in brain tumors.Theranostics · 2025Review
- Advances of E3 ligases in lung cancer.Biochemistry and biophysics reports · 2024Review
- Design and Characterization of a Novel eEF2K Degrader with Potent Therapeutic Efficacy Against Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Diallyl disulfide induces DNA damage and growth inhibition in colorectal cancer cells by promoting POU2F1 ubiquitination.International journal of biological sciences · 2024Article
- Caprin-1 influences autophagy-induced tumor growth and immune modulation in pancreatic cancer.Journal of translational medicine · 2023Article
- The SUMOylation and ubiquitination crosstalk in cancer.Journal of cancer research and clinical oncology · 2023Review
- The emerging roles of SUMOylation in pulmonary diseases.Molecular medicine (Cambridge, Mass.) · 2023Review
- SUMO1 degrader induces ER stress and ROS accumulation through deSUMOylation of TCF4 and inhibition of its transcription of StarD7 in colon cancer.Molecular carcinogenesis · 2023Article
- Paradoxes of Cellular SUMOylation Regulation: A Role of Biomolecular Condensates?Pharmacological reviews · 2023Review
- Cullin-associated and neddylation-dissociated protein 1 (CAND1) alleviates NAFLD by reducing ubiquitinated degradation of ACAA2.Nature communications · 2023Article
- Review
- The association and clinical relevance of phase-separating protein CAPRIN1 with noncoding RNA.Cell stress & chaperones · 2023Review
- Positioning SUMO as an immunological facilitator of oncolytic viruses for high-grade glioma.Frontiers in cell and developmental biology · 2023Review
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Authors and funding
19 authors.
Funding
Abstract
Discovery of small-molecule degraders that activate ubiquitin ligase–mediated ubiquitination and degradation of targeted oncoproteins in cancer cells has been an elusive therapeutic strategy. Here, we report a cancer cell–based drug screen of the NCI drug-like compounds library that enabled identification of small-molecule degraders of the small ubiquitin-related modifier 1 (SUMO1). Structure-activity relationship studies of analogs of the hit compound CPD1 led to identification of a lead compound HB007 with improved properties and anticancer potency in vitro and in vivo. A genome-scale CRISPR-Cas9 knockout screen identified the substrate receptor F-box protein 42 (FBXO42) of cullin 1 (CUL1) E3 ubiquitin ligase as required for HB007 activity. Using HB007 pull-down proteomics assays, we pinpointed HB007’s binding protein as the cytoplasmic activation/proliferation-associated protein 1 (CAPRIN1). Biolayer interferometry and compound competitive immunoblot assays confirmed the selectivity of HB007’s binding to CAPRIN1. When bound to CAPRIN1, HB007 induced the interaction of CAPRIN1 with FBXO42. FBXO42 then recruited SUMO1 to the CAPRIN1-CUL1-FBXO42 ubiquitin ligase complex, where SUMO1 was ubiquitinated in several of human cancer cells. HB007 selectively degraded SUMO1 in patient tumor–derived xenografts implanted into mice. Systemic administration of HB007 inhibited the progression of patient-derived brain, breast, colon, and lung cancers in mice and increased survival of the animals. This cancer cell–based screening approach enabled discovery of a small-molecule degrader of SUMO1 and may be useful for identifying other small-molecule degraders of oncoproteins.
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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.