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Good Cop, Bad Cop: Defining the Roles of Δ40p53 in Cancer and Aging

1
Priority Research Centre for Cancer Research, Innovation and Translation, School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Newcastle, NSW 2305, Australia
2
Hunter Cancer Research Alliance, Newcastle, NSW 2305, Australia
3
Hunter Medical Research Institute, Newcastle, NSW 2305, Australia
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Department of Biochemistry and Molecular Biology, Medical University of Lublin, 20-093 Lublin, Poland
5
Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, Faculty of Science, University of Newcastle, Callaghan, Newcastle, NSW 2308, Australia
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(6), 1659; https://doi.org/10.3390/cancers12061659
Received: 25 May 2020 / Revised: 11 June 2020 / Accepted: 18 June 2020 / Published: 23 June 2020
The tumour suppressor p53 is essential for maintaining DNA integrity, and plays a major role in cellular senescence and aging. Understanding the mechanisms that contribute to p53 dysfunction can uncover novel possibilities for improving cancer therapies and diagnosis, as well as cognitive decline associated with aging. In recent years, the complexity of p53 signalling has become increasingly apparent owing to the discovery of the p53 isoforms. These isoforms play important roles in regulating cell growth and turnover in response to different stressors, depending on the cellular context. In this review, we focus on Δ40p53, an N-terminally truncated p53 isoform. Δ40p53 can alter p53 target gene expression in both a positive and negative manner, modulating the biological outcome of p53 activation; it also functions independently of p53. Therefore, proper control of the Δ40p53: p53 ratio is essential for normal cell growth, aging, and responses to cancer therapy. Defining the contexts and the mechanisms by which Δ40p53 behaves as a “good cop or bad cop” is critical if we are to target this isoform therapeutically. View Full-Text
Keywords: p53 isoforms; Δ40p53; p53; cancer; aging p53 isoforms; Δ40p53; p53; cancer; aging
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MDPI and ACS Style

Steffens Reinhardt, L.; Zhang, X.; Wawruszak, A.; Groen, K.; De Iuliis, G.N.; Avery-Kiejda, K.A. Good Cop, Bad Cop: Defining the Roles of Δ40p53 in Cancer and Aging. Cancers 2020, 12, 1659.

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