Abstract
Pathogenic aggregation is closely associated with various protein misfolding diseases such as type 2 diabetes mellitus and Alzheimer's disease. Amyloidogenic proteins that have a propensity to assemble into amyloid oligomers and fibrils form the aggregates. The tumor suppressor p53, a transcription factor that regulates the cell cycle and apoptosis, is also amyloidogenic. In tumor models, both wild type and mutant p53 proteins show aggregation kinetics and morphology similar to those of classical amyloidogenic proteins, such as β-amyloid peptide and α- synuclein. Wild type p53 loses its anticancer activity when it aggregates, while p53 mutants with enhanced amyloidogenicity show accelerated aggregation. So far, amyloidogenic p53 mutations have been implicated in more than ten different types of cancer, suggesting a connection between p53 aggregation and cancer. Therefore, inhibition of both inherent and mutation induced p53 aggregation may stabilize p53 in a functional conformation and provide a novel approach to cancer prevention and treatment. Here, we summarize recent findings on carcinogenic aggregation of wild type p53 and its clinical mutants, structure-dependent amyloidogenesis of p53, and several promising strategies based on inhibition of p53 aggregation are also discussed.
Keywords: amyloid, cancer, mutant p53, p53, protein aggregation.
Current Protein & Peptide Science
Title:Amyloidogenicity of p53: A Hidden Link Between Protein Misfolding and Cancer
Volume: 16 Issue: 2
Author(s): Hao Gong, Xin Yang, Yudan Zhao, Robert B. Petersen, Xinran Liu, Yang Liu and Kun Huang
Affiliation:
Keywords: amyloid, cancer, mutant p53, p53, protein aggregation.
Abstract: Pathogenic aggregation is closely associated with various protein misfolding diseases such as type 2 diabetes mellitus and Alzheimer's disease. Amyloidogenic proteins that have a propensity to assemble into amyloid oligomers and fibrils form the aggregates. The tumor suppressor p53, a transcription factor that regulates the cell cycle and apoptosis, is also amyloidogenic. In tumor models, both wild type and mutant p53 proteins show aggregation kinetics and morphology similar to those of classical amyloidogenic proteins, such as β-amyloid peptide and α- synuclein. Wild type p53 loses its anticancer activity when it aggregates, while p53 mutants with enhanced amyloidogenicity show accelerated aggregation. So far, amyloidogenic p53 mutations have been implicated in more than ten different types of cancer, suggesting a connection between p53 aggregation and cancer. Therefore, inhibition of both inherent and mutation induced p53 aggregation may stabilize p53 in a functional conformation and provide a novel approach to cancer prevention and treatment. Here, we summarize recent findings on carcinogenic aggregation of wild type p53 and its clinical mutants, structure-dependent amyloidogenesis of p53, and several promising strategies based on inhibition of p53 aggregation are also discussed.
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Cite this article as:
Gong Hao, Yang Xin, Zhao Yudan, Petersen B. Robert, Liu Xinran, Liu Yang and Huang Kun, Amyloidogenicity of p53: A Hidden Link Between Protein Misfolding and Cancer, Current Protein & Peptide Science 2015; 16 (2) . https://dx.doi.org/10.2174/1389203715666141128115649
DOI https://dx.doi.org/10.2174/1389203715666141128115649 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
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