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p53 Isoforms in Cellular Senescence- and Ageing-Associated Biological and Physiological Functions

Cell Induction and Regulation Field, Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
Int. J. Mol. Sci. 2019, 20(23), 6023; https://doi.org/10.3390/ijms20236023
Received: 30 October 2019 / Revised: 22 November 2019 / Accepted: 27 November 2019 / Published: 29 November 2019
(This article belongs to the Special Issue p53 in Cancer and beyond—40 Years after Its Discovery)
Cellular senescence, a term originally used to define the characteristics of normal human fibroblasts that reached their replicative limit, is an important factor for ageing, age-related diseases including cancer, and cell reprogramming. These outcomes are mediated by senescence-associated changes in gene expressions, which sometimes lead to the secretion of pro-inflammatory factors, or senescence-associated secretory phenotype (SASP) that contribute to paradoxical pro-tumorigenic effects. p53 functions as a transcription factor in cell-autonomous responses such as cell-cycle control, DNA repair, apoptosis, and cellular senescence, and also non-cell-autonomous responses to DNA damage by mediating the SASP function of immune system activation. The human TP53 gene encodes twelve protein isoforms, which provides an explanation for the pleiotropic p53 function on cellular senescence. Recent reports suggest that some short isoforms of p53 may modulate gene expressions in a full-length p53-dependent and -independent manner, in other words, some p53 isoforms cooperate with full-length p53, whereas others operate independently. This review summarizes our current knowledge about the biological activities and functions of p53 isoforms, especially Δ40p53, Δ133p53α, and p53β, on cellular senescence, ageing, age-related disorder, reprogramming, and cancer. Numerous cellular and animal model studies indicate that an unbalance in p53 isoform expression in specific cell types causes age-related disorders such as cancer, premature ageing, and degenerative diseases. View Full-Text
Keywords: p53 isoform; cellular senescence; ageing and age-related diseases; reprogramming; cancer p53 isoform; cellular senescence; ageing and age-related diseases; reprogramming; cancer
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MDPI and ACS Style

Fujita, K. p53 Isoforms in Cellular Senescence- and Ageing-Associated Biological and Physiological Functions. Int. J. Mol. Sci. 2019, 20, 6023. https://doi.org/10.3390/ijms20236023

AMA Style

Fujita K. p53 Isoforms in Cellular Senescence- and Ageing-Associated Biological and Physiological Functions. International Journal of Molecular Sciences. 2019; 20(23):6023. https://doi.org/10.3390/ijms20236023

Chicago/Turabian Style

Fujita, Kaori. 2019. "p53 Isoforms in Cellular Senescence- and Ageing-Associated Biological and Physiological Functions" International Journal of Molecular Sciences 20, no. 23: 6023. https://doi.org/10.3390/ijms20236023

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