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• W3135014513 endingPage "381" @default.
• W3135014513 startingPage "381" @default.
• W3135014513 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." @default.
• W3135014513 created "2021-03-15" @default.
• W3135014513 creator A5028237788 @default.
• W3135014513 creator A5053727563 @default.
• W3135014513 creator A5081208395 @default.
• W3135014513 creator A5089660142 @default.
• W3135014513 date "2021-03-04" @default.
• W3135014513 modified "2023-10-14" @default.
• W3135014513 title "Mutations of Intrinsically Disordered Protein Regions Can Drive Cancer but Lack Therapeutic Strategies" @default.
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