ArticleNature cell biology2020
A pan-cancer analysis reveals nonstop extension mutations causing SMAD4 tumour suppressor degradation.
Article in Nature cell biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- Meeting Review on India EMBO lecture course on RNA-protein complexes: from molecular assembly to physiological functions and disease.Biology open · 2026Article
- Protein C-terminal variations impact proteostasis.Nature communications · 2026Article
- Association of SMAD4 gene polymorphisms with human papillomavirus infection and risk of cervical cancer: a case-control study.BMC cancer · 2026Article
- A predictive framework for stop-loss variants with C-terminal extensions.Nucleic acids research · 2026Article
- Degrons: defining the rules of protein degradation.Nature reviews. Molecular cell biology · 2025Review
- Mechanisms suppressing noncoding translation.Trends in cell biology · 2025Review
- Massive mutagenesis reveals an incomplete amyloid motif in Bri2 that turns amyloidogenic upon C-terminal extension.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Nonstop mutations cause loss of renal tumor suppressor proteinsScience advances · 2025Article
- Delineating the roles of HOXB13 X285K variant in prostate cancer.Serican journal of medicine · 2025Article
- Suppressive cancer nonstop extension mutations increase C-terminal hydrophobicity and disrupt evolutionarily conserved amino acid patterns.Nature communications · 2024Article
- Hominini-specific regulation of the cell cycle by stop codon readthrough of FEM1B.Journal of cell science · 2024Article
- Underlying effect of SMAD4 gene polymorphism on risk prediction of papillary thyroid carcinoma in Chinese population.Heliyon · 2024Article
- Constructing gene similarity networks using co-occurrence probabilities.BMC genomics · 2023Article
- Target-dependent RNA polymerase as universal platform for gene expression control in response to intracellular molecules.Nature communications · 2023Article
- Control of TGFβ signalling by ubiquitination independent function of E3 ubiquitin ligase TRIP12.Cell death & disease · 2023Article
- Article
- Noncoding translation mitigation.Nature · 2023Article
- Chimeric oligonucleotides combining guide RNA and single-stranded DNA repair template effectively induce precision gene editing.RNA biology · 2022Article
- Systematic analysis of migration factors by MigExpress identifies essential cell migration control genes in non-small cell lung cancer.Molecular oncology · 2021Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nonstop or stop-loss mutations convert a stop into a sense codon, resulting in translation into the 3' untranslated region as a nonstop extension mutation to the next in-frame stop codon or as a readthrough mutation into the poly-A tail. Nonstop mutations have been characterized in hereditary diseases, but not in cancer genetics. In a pan-cancer analysis, we curated and analysed 3,412 nonstop mutations from 62 tumour entities, generating a comprehensive database at http://NonStopDB.dkfz.de. Six different nonstop extension mutations affected the tumour suppressor SMAD4, extending its carboxy terminus by 40 amino acids. These caused rapid degradation of the SMAD4 mutants via the ubiquitin-proteasome system. A hydrophobic degron signal sequence of ten amino acids within the carboxy-terminal extension was required to induce complete loss of the SMAD4 protein. Thus, we discovered that nonstop mutations can be functionally important in cancer and characterize their loss-of-function impact on the tumour suppressor SMAD4.
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