p53 Isoforms and Their Implications in Cancer

In this review we focus on the major isoforms of the tumor-suppressor protein p53, dysfunction of which often leads to cancer. Mutations of the TP53 gene, particularly in the DNA binding domain, have been regarded as the main cause for p53 inactivation. However, recent reports demonstrating abundanc...

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Main Authors: Maximilian Vieler, Suparna Sanyal
Format: Article
Language:English
Published: MDPI AG 2018-08-01
Series:Cancers
Subjects:
Online Access:http://www.mdpi.com/2072-6694/10/9/288
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author Maximilian Vieler
Suparna Sanyal
author_facet Maximilian Vieler
Suparna Sanyal
author_sort Maximilian Vieler
collection DOAJ
description In this review we focus on the major isoforms of the tumor-suppressor protein p53, dysfunction of which often leads to cancer. Mutations of the TP53 gene, particularly in the DNA binding domain, have been regarded as the main cause for p53 inactivation. However, recent reports demonstrating abundance of p53 isoforms, especially the N-terminally truncated ones, in the cancerous tissues suggest their involvement in carcinogenesis. These isoforms are ∆40p53, ∆133p53, and ∆160p53 (the names indicate their respective N-terminal truncation). Due to the lack of structural and functional characterizations the modes of action of the p53 isoforms are still unclear. Owing to the deletions in the functional domains, these isoforms can either be defective in DNA binding or more susceptive to altered ‘responsive elements’ than p53. Furthermore, they may exert a ‘dominant negative effect’ or induce more aggressive cancer by the ‘gain of function’. One possible mechanism of p53 inactivation can be through tetramerization with the ∆133p53 and ∆160p53 isoforms—both lacking part of the DNA binding domain. A recent report and unpublished data from our laboratory also suggest that these isoforms may inactivate p53 by fast aggregation—possibly due to ectopic overexpression. We further discuss the evolutionary significance of the p53 isoforms.
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spelling doaj.art-fb44149bc016425dbd5b116352a135db2023-09-02T21:22:10ZengMDPI AGCancers2072-66942018-08-0110928810.3390/cancers10090288cancers10090288p53 Isoforms and Their Implications in CancerMaximilian Vieler0Suparna Sanyal1Department of Cell and Molecular Biology, Uppsala University, Box-596, BMC, Uppsala SE-75124, SwedenDepartment of Cell and Molecular Biology, Uppsala University, Box-596, BMC, Uppsala SE-75124, SwedenIn this review we focus on the major isoforms of the tumor-suppressor protein p53, dysfunction of which often leads to cancer. Mutations of the TP53 gene, particularly in the DNA binding domain, have been regarded as the main cause for p53 inactivation. However, recent reports demonstrating abundance of p53 isoforms, especially the N-terminally truncated ones, in the cancerous tissues suggest their involvement in carcinogenesis. These isoforms are ∆40p53, ∆133p53, and ∆160p53 (the names indicate their respective N-terminal truncation). Due to the lack of structural and functional characterizations the modes of action of the p53 isoforms are still unclear. Owing to the deletions in the functional domains, these isoforms can either be defective in DNA binding or more susceptive to altered ‘responsive elements’ than p53. Furthermore, they may exert a ‘dominant negative effect’ or induce more aggressive cancer by the ‘gain of function’. One possible mechanism of p53 inactivation can be through tetramerization with the ∆133p53 and ∆160p53 isoforms—both lacking part of the DNA binding domain. A recent report and unpublished data from our laboratory also suggest that these isoforms may inactivate p53 by fast aggregation—possibly due to ectopic overexpression. We further discuss the evolutionary significance of the p53 isoforms.http://www.mdpi.com/2072-6694/10/9/288p53cancerp53 isoform∆133p53∆160p53∆40p53aggregationprion
spellingShingle Maximilian Vieler
Suparna Sanyal
p53 Isoforms and Their Implications in Cancer
Cancers
p53
cancer
p53 isoform
∆133p53
∆160p53
∆40p53
aggregation
prion
title p53 Isoforms and Their Implications in Cancer
title_full p53 Isoforms and Their Implications in Cancer
title_fullStr p53 Isoforms and Their Implications in Cancer
title_full_unstemmed p53 Isoforms and Their Implications in Cancer
title_short p53 Isoforms and Their Implications in Cancer
title_sort p53 isoforms and their implications in cancer
topic p53
cancer
p53 isoform
∆133p53
∆160p53
∆40p53
aggregation
prion
url http://www.mdpi.com/2072-6694/10/9/288
work_keys_str_mv AT maximilianvieler p53isoformsandtheirimplicationsincancer
AT suparnasanyal p53isoformsandtheirimplicationsincancer