Data for: Investigating the aggregation and prionogenic properties of human cancer-related proteins
Data files
Mar 14, 2025 version files 1.51 MB
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README.md
994 B
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Table_S1.csv
1.49 MB
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Table_S2.csv
11.61 KB
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Table_S3.csv
4.93 KB
Abstract
Cancer encompasses a range of severe diseases characterized by uncontrolled cell growth and the potential for metastasis. Understanding the mechanism underlying tumorigenesis has been a central focus of cancer research. Self-propagating protein aggregates, known as prions, are linked to various biological functions and diseases, particularly those related to mammalian neurodegeneration. However, it remains unclear whether prion-like mechanisms contribute to tumorigenesis and cancer. Using a combined approach of algorithmic predictions, alongside genetic and biochemical experimentation, we identified numerous cancer-associated proteins prone to aggregation, many of which contain prion-like domains (PrLDs). These predictions were experimentally validated for both aggregation and prion-formation. We demonstrate that several PrLDs undergo nucleation-limited amyloid formation, which can alter protein activity in a mitotically heritable fashion. These include SSXT, a subunit of the chromatin-remodeling BAF (hSWI/SNF) complexes; CLOCK, a core component of the circadian clock; and EPN4, a clathrin-interacting protein involved in protein trafficking between the trans-Golgi network and endosomes. The prions formed by these PrLDs occurred in multiple variants and depended on Hsp104, a molecular chaperone with disaggregase activity. Our results reveal an inherent tendency for prion-like aggregation in human cancer-associated proteins, suggesting a potential role for such aggregation in the epigenetic changes driving tumorigenesis.
https://doi.org/10.5061/dryad.905qfttw0
Description of the data and file structure
Table S1 shows computational analysis results to rank the aggregation propensity and prionogenicity of 9620 cancer-associated human proteins in this study. In the csv data sheet, FI MaxRun, PASTA Energy, and PASTA Disorder are for folding/free energy/disorder; and PLAAC Score and PAPA Score are used to measure the prionogenicity of a PrLD. Columns D-H are for normalized scores (0-1) and column I is weighted score - average of the normalized scores with distinct weighting factors considering equal importance of folding/free energy/disorder and prionogenicity. Table S2 and S3 include information of plasmids and primers used in this study, respectively. N/A, information unavailable.
Code/software
Microsoft Office Excel or .cvs combatable programs.