ArticleBiomolecules2021
Mutations of Intrinsically Disordered Protein Regions Can Drive Cancer but Lack Therapeutic Strategies.
Article in Biomolecules, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- Pathogenic variations illuminate functional constraints in intrinsically disordered proteins.iScience · 2026Article
- A Survey of Predicted Protein-Protein Interactions Involving Disordered Regions in Humans.Journal of molecular biology · 2026Article
- Unleashed condensation by recurrent mutations of an epigenetic regulator promotes cancer.bioRxiv : the preprint server for biology · 2026Article
- MarkerPredict: predicting clinically relevant predictive biomarkers with machine learning.NPJ systems biology and applications · 2025Article
- SETBP1 variants outside the degron disrupt DNA-binding, transcription and neuronal differentiation capacity to cause a heterogeneous neurodevelopmental disorder.Nature communications · 2025Article
- Phase-separating fusion proteins drive cancer by upsetting transcription regulation.Genome biology · 2025Article
- Targeting protein disorder: the next hurdle in drug discovery.Nature reviews. Drug discovery · 2025Review
- Energy Landscapes and Structural Plasticity of Intrinsically Disordered Histones.Journal of chemical information and modeling · 2025Article
- Bioinformatics-Based Comparative Analysis of the Human Retina Proteome.Proteomics. Clinical applications · 2025Article
- Umbrella Refinement of Ensembles-An Alternative View of Ensemble Optimization.Molecules (Basel, Switzerland) · 2025Article
- Decoding the functional impact of the cancer genome through protein-protein interactions.Nature reviews. Cancer · 2025Review
- Neurogenic locus notch homolog protein 1 (NOTCH 1) SNP informatics coupled with intrinsically disordered regions and post-translational modifications reveals the complex structural crosstalk of Lung Adenocarcinoma (LUAD).Frontiers in bioinformatics · 2025Article
- DEMINING: A deep learning model embedded framework to distinguish RNA editing from DNA mutations in RNA sequencing data.Genome biology · 2024Article
- Structural analysis of genomic and proteomic signatures reveal dynamic expression of intrinsically disordered regions in breast cancer.iScience · 2024Article
- Proteome-scale characterisation of motif-based interactome rewiring by disease mutations.Molecular systems biology · 2024Article
- Pathogenic mutations of human phosphorylation sites affect protein-protein interactions.Nature communications · 2024Article
- The molecular basis for cellular function of intrinsically disordered protein regions.Nature reviews. Molecular cell biology · 2024Review
- Tutorial: a guide for the selection of fast and accurate computational tools for the prediction of intrinsic disorder in proteins.Nature protocols · 2023Review
- Intrinsic disorder may drive the interaction of PROS1 and MERTK in uveal melanoma.International journal of biological macromolecules · 2023Article
- Interaction modules that impart specificity to disordered protein.Trends in biochemical sciences · 2023Review
Corrections and comments
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4 authors.
Funding
Abstract
Many proteins contain intrinsically disordered regions (IDRs) which carry out important functions without relying on a single well-defined conformation. IDRs are increasingly recognized as critical elements of regulatory networks and have been also associated with cancer. However, it is unknown whether mutations targeting IDRs represent a distinct class of driver events associated with specific molecular and system-level properties, cancer types and treatment options. Here, we used an integrative computational approach to explore the direct role of intrinsically disordered protein regions driving cancer. We showed that around 20% of cancer drivers are primarily targeted through a disordered region. These IDRs can function in multiple ways which are distinct from the functional mechanisms of ordered drivers. Disordered drivers play a central role in context-dependent interaction networks and are enriched in specific biological processes such as transcription, gene expression regulation and protein degradation. Furthermore, their modulation represents an alternative mechanism for the emergence of all known cancer hallmarks. Importantly, in certain cancer patients, mutations of disordered drivers represent key driving events. However, treatment options for such patients are currently severely limited. The presented study highlights a largely overlooked class of cancer drivers associated with specific cancer types that need novel therapeutic options.
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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.