ArticleMolecular cell2021
Systematic characterization of mutations altering protein degradation in human cancers.
Article in Molecular cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 84 citations in OpenAlex.
- Unsupervised discovery of functional sequence patterns from protein language model with MotifAE.Nature communications · 2026Article
- Pan-cancer proteogenomic interrogation of the ubiquitin-proteasome system.Cell death and differentiation · 2026Article
- Deep learning-driven decoding of ubiquitination: from regulatory mechanisms to targeted protein degradation.Biology direct · 2026Review
- Pan-cancer proteogenomic interrogation of the Ubiquitin Proteasome System.bioRxiv : the preprint server for biology · 2026Article
- Actually, what is a gain-of-function mutation?Genetics · 2026Article
- Mechanisms and Design Principles of Proteolysis-Targeting Chimeras and Their Emerging Applications.ACS pharmacology & translational science · 2026Review
- Degrons and degradation signals beyond short linear motifs.Nature chemical biology · 2026Review
- Proteasomal control of transcription factors: mechanisms, regulation and dysregulation.Cellular and molecular life sciences : CMLS · 2026Review
- A near-complete map of human cytosolic degrons and their relevance for disease.Science advances · 2026Article
- From concept to application: Exploring the evolution and potential of DUBTAC technology.Acta pharmaceutica Sinica. B · 2026Review
- Article
- Innovative Therapies for Oncogenic KRAS Mutations: Precision Strategies with PROTACs in Cancer Treatment.Anti-cancer agents in medicinal chemistry · 2026Review
- Cancer degronopathies and protein-fate biomarkers in drug resistance and cancer progression: signalling mechanisms, measurement and translational limits.Frontiers in cell and developmental biology · 2026Review
- From locus to gene: causal inference and experimental validation prioritize PSMA4 as a candidate target in lung adenocarcinoma.American journal of cancer research · 2026Article
- Dysregulation of the ubiquitin-proteasome system in von Hippel-Lindau syndrome: molecular insights and clinical perspectives.Clinical and experimental medicine · 2025Review
- Degrons: defining the rules of protein degradation.Nature reviews. Molecular cell biology · 2025Review
- MARCH1, transcriptionally regulated by POU2F2, facilitates acute myeloid leukemia progression via inducing MYCT1 degradation.Oncogene · 2025Article
- VaMIEL1-mediated ubiquitination of VaMYB4a orchestrates cold tolerance through integrated transcriptional and oxidative stress pathways in grapevine.Horticulture research · 2025Article
- GID4 recognition of Pro/N-degron peptides: Conformational selection and induced fit.Biophysical journal · 2025Article
- Sequence rules for a long SPOP-binding degron required for protein ubiquitylation.The Biochemical journal · 2025Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
The ubiquitin-proteasome system (UPS) is the primary route for selective protein degradation in human cells. The UPS is an attractive target for novel cancer therapies, but the precise UPS genes and substrates important for cancer growth are incompletely understood. Leveraging multi-omics data across more than 9,000 human tumors and 33 cancer types, we found that over 19% of all cancer driver genes affect UPS function. We implicate transcription factors as important substrates and show that c-Myc stability is modulated by CUL3. Moreover, we developed a deep learning model (deepDegron) to identify mutations that result in degron loss and experimentally validated the prediction that gain-of-function truncating mutations in GATA3 and PPM1D result in increased protein stability. Last, we identified UPS driver genes associated with prognosis and the tumor microenvironment. This study demonstrates the important role of UPS dysregulation in human cancer and underscores the potential therapeutic utility of targeting the UPS.
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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.