title: p53 Isoforms: Key Regulators of the Cell Fate Decision.
abstract: It is poorly understood how a single protein, p53, can be responsive to so many stress signals and orchestrates very diverse cell responses to maintain/restore cell/tissue functions. The uncovering that TP53 gene physiologically expresses, in a tissue-dependent manner, several p53 splice variants (isoforms) provides an explanation to its pleiotropic biological activities. Here, we summarize a decade of research on p53 isoforms. The clinical studies and the diverse cellular and animal models of p53 isoforms (zebrafish, Drosophila, and mouse) lead us to realize that a p53-mediated cell response is, in fact, the sum of the intrinsic activities of the coexpressed p53 isoforms and that unbalancing expression of different p53 isoforms leads to cancer, premature aging, (neuro)degenerative diseases, inflammation, embryo malformations, or defects in tissue regeneration. Cracking the p53 isoforms' code is, thus, a necessary step to improve cancer treatment. It also opens new exciting perspectives in tissue regeneration.
authors.affiliation: Dundee Cancer Centre, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, United Kingdom.
authors.forename: Sebastien M
authors.initials: SM
authors.lastname: Joruiz
authors.affiliation: Dundee Cancer Centre, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, United Kingdom.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Bourdon
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology; D004330:Drosophila / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53 / Q000502:physiology*; D006801:Humans; D051379:Mice / Q000235:genetics; D023421:Models, Animal; D009369:Neoplasms / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D015027:Zebrafish / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D020033:Protein Isoforms; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53