ArticleNature cell biology2009
UBE2S elongates ubiquitin chains on APC/C substrates to promote mitotic exit.
Article in Nature cell biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 168 papers.
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Who cites it
168 citing papers in PubMed, 246 citations in OpenAlex.
- MAD2L1 overexpression promotes breast cancer progression and confers resistance to paclitaxel via proteasomal stabilization.Oncology letters · 2026Article
- Structural determinants for FAT10 activation and transfer from UBA6 to E2 enzymes.Nature communications · 2026Article
- FOXM1 Signaling Network Transcriptionally Upregulates Expression of Proteins Involved in Mitotic Progression to Induce High Proliferation and Chromosomal Instability in Androgen Receptor-Low Triple-Negative Breast Cancer.International journal of molecular sciences · 2026Article
- Systemic responses to intravenous rAAV administration in boys with Duchenne muscular dystrophy.Frontiers in molecular medicine · 2026Article
- The Ubiquitin Script: writing protein fates in chains.Essays in biochemistry · 2025Review
- The deubiquitinating enzyme Cezanne stabilizes BRCA1 by counteracting APC/C and Ube2S-dependent Lys11-linked ubiquitination.PLoS biology · 2025Article
- Gut Microbial Postbiotics as Potential Therapeutics for Lymphoma: Proteomics Insights of the Synergistic Effects of Nisin and Urolithin B Against Human Lymphoma Cells.International journal of molecular sciences · 2025Article
- FERMT2 drives anoikis resistance and peritoneal metastasis by enhancing extracellular matrix deposition in gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2025Article
- APC/C-mediated ubiquitylation of extranucleosomal histone complexes lacking canonical degrons.Nature communications · 2025Article
- Prognostic Value of UBE2S, HIF-1α, and FOXM1 Expression in Esophageal Squamous Cell Carcinoma.Analytical cellular pathology (Amsterdam) · 2025Article
- A comparative study of the cryo-EM structures ofeLife · 2024Article
- Targeted protein degradation using chimeric human E2 ubiquitin-conjugating enzymes.Communications biology · 2024Article
- FAS Inhibited Proteomics and Phosphoproteomics Profiling of Colorectal Cancer Spheroids Shows Activation of Ferroptotic Death Mechanism.Journal of proteome research · 2024Article
- OTUD5 promotes the inflammatory immune response by enhancing MyD88 oligomerization and Myddosome formation.Cell death and differentiation · 2024Article
- [High expression of UBE2S promotes progression of hepatocellular carcinoma by increasing cancer cell stemness].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Weakened APC/C activity at mitotic exit drives cancer vulnerability to KIF18A inhibition.The EMBO journal · 2024Article
- Diverse roles of UBE2S in cancer and therapy resistance: Biological functions and mechanisms.Heliyon · 2024Review
- Genetic Changes in Mastocytes and Their Significance in Mast Cell Tumor Prognosis and Treatment.Genes · 2024Review
- Time-resolved cryo-EM (TR-EM) analysis of substrate polyubiquitination by the RING E3 anaphase-promoting complex/cyclosome (APC/C).Nature structural & molecular biology · 2023Article
- Function, mechanism and drug discovery of ubiquitin and ubiquitin-like modification with multiomics profiling for cancer therapy.Acta pharmaceutica Sinica. B · 2023Review
108 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
The anaphase-promoting complex (APC/C), a ubiquitin ligase, is the target of the spindle-assembly checkpoint (SAC), and it ubiquitylates protein substrates whose degradation regulates progress through mitosis. The identity of the ubiquitin-conjugating (E2) enzymes that work with the APC/C is unclear. In an RNA interference (RNAi) screen for factors that modify release from drug-induced SAC activation, we identified the E2 enzyme UBE2S as an APC/C auxiliary factor that promotes mitotic exit. UBE2S is dispensable in a normal mitosis, but its depletion prolongs drug-induced mitotic arrest and suppresses mitotic slippage. In vitro, UBE2S elongates ubiquitin chains initiated by the E2 enzymes UBCH10 and UBCH5, enhancing the degradation of APC/C substrates by the proteasome. Indeed, following release from SAC-induced mitotic arrest, UBE2S-depleted cells neither degrade crucial APC/C substrates, nor silence this checkpoint, whereas bypassing the SAC through BUBR1 depletion or Aurora-B inhibition negates the requirement for UBE2S. Thus, UBE2S functions with the APC/C in a two-step mechanism to control substrate ubiquitylation that is essential for mitotic exit after prolonged SAC activation, providing a new model for APC/C function in human cells.
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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.