Expanding the prion concept to cancer biology: dominant-negative effect of aggregates of mutant p53 tumour suppressor. Issue 4 (25th July 2013)

• Record Type: Journal Article
• Authors: Silva, Jerson L.; Rangel, Luciana P.; Costa, Danielly C. F.; Cordeiro, Yraima; De Moura Gallo, Claudia V.
• Is Part Of: Bioscience reports. Volume 33:Issue 4(2013)
• Publication Date: 2013-07-25
• Subjects: amyloid -- cancer -- p53 -- prions -- protein aggregation -- protein misfolding; Molecular biology -- Periodicals; Cytology -- Periodicals; 572.8
• DOI: 10.1042/BSR20130065
• Languages: English
• ISSNs: 0144-8463

Abstract

Abstract : p53 is a key protein that participates in cell-cycle control, and its malfunction can lead to cancer. This tumour suppressor protein has three main domains; the N-terminal transactivation domain, the CTD (C-terminal domain) and the core domain (p53C) that constitutes the sequence-specific DBD (DNA-binding region). Most p53 mutations related to cancer development are found in the DBD. Aggregation of p53 into amyloid oligomers and fibrils has been shown. Moreover, amyloid aggregates of both the mutant and WT (wild-type) forms of p53 were detected in tumour tissues. We propose that if p53 aggregation occurred, it would be a crucial aspect of cancer development, as p53 would lose its WT functions in an aggregated state. Mutant p53 can also exert a dominant-negative regulatory effect on WT p53. Herein, we discuss the dominant-negative effect in light of p53 aggregation and the fact that amyloid-like mutant p53 can convert WT p53 into more aggregated species, leading into gain of function in addition to the loss of tumour suppressor function. In summary, the results obtained in the last decade indicate that cancer may have characteristics in common with amyloidogenic and prion diseases.