학술논문

Biological functions of p53 isoforms through evolution: lessons from animal and cellular models.
Document Type
Article
Source
Cell Death & Differentiation. Dec2011, Vol. 18 Issue 12, p1815-1824. 10p. 3 Diagrams, 2 Charts.
Subject
*ANIMAL models in research
*P53 protein
*TUMOR suppressor genes
*APOPTOSIS
*CELL cycle
*BIOMARKERS
*ANIMAL models of cancer
Language
ISSN
1350-9047
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. [ABSTRACT FROM AUTHOR]