title: Biological functions of p53 isoforms through evolution: lessons from animal and cellular models.
abstract: The TP53 tumour-suppressor gene is expressed as several protein isoforms generated by different mechanisms, including use of alternative promoters, splicing sites and translational initiation sites, that are conserved through evolution and within the TP53 homologues, TP63 and TP73. Although first described in the eighties, the importance of p53 isoforms in regulating the suppressive functions of p53 has only become evident in the last 10 years, by analogy with observations that p63 and p73 isoforms appeared indispensable to fully understand the biological functions of TP63 and TP73. This review summarizes recent advances in the field of 'p53 isoforms', including new data on p63 and p73 isoforms. Details of the alternative mechanisms that produce p53 isoforms and cis- and trans-regulators identified are provided. The main focus is on their biological functions (apoptosis, cell cycle, aging and so on) in cellular and animal models, including mouse, zebrafish and Drosophila. Finally, the deregulation of p53 isoform expression in human cancers is reviewed. Based on these latest results, several developments are expected in the future: the identification of drugs modulating p53 isoform expression; the generation of animal models and the evaluation of the use of p53 isoform as biomarkers in human cancers.
authors.affiliation: Centre for Oncology and Molecular Medicine, INSERM-European Associated Laboratory, University of Dundee, Ninewells Hospital, Dundee, Scotland, UK.
authors.forename: V
authors.initials: V
authors.lastname: Marcel
authors.forename: M-L
authors.initials: ML
authors.lastname: Dichtel-Danjoy
authors.forename: C
authors.initials: C
authors.lastname: Sagne
authors.forename: H
authors.initials: H
authors.lastname: Hafsi
authors.forename: D
authors.initials: D
authors.lastname: Ma
authors.forename: S
authors.initials: S
authors.lastname: Ortiz-Cuaran
authors.forename: M
authors.initials: M
authors.lastname: Olivier
authors.forename: J
authors.initials: J
authors.lastname: Hall
authors.forename: B
authors.initials: B
authors.lastname: Mollereau
authors.forename: P
authors.initials: P
authors.lastname: Hainaut
authors.forename: J-C
authors.initials: JC
authors.lastname: Bourdon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004195:Disease Models, Animal; D019143:Evolution, Molecular; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009369:Neoplasms / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology
chemical_list: D020033:Protein Isoforms; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins