The p53 family of proteins evolved from a common ancestor into three separate genes encoding proteins that act as transcription factors with distinct cellular roles. Isoforms of each member that lack specific regions or domains are suggested to result from alternative transcription start sites, alternative splicing or alternative translation initiation, and have the potential to exponentially increase the functional repertoire of each gene. However, evidence supporting the presence of individual protein variants at functional levels is often limited and is inferred by mRNA detection using highly sensitive amplification techniques. We provide a critical appraisal of the current evidence for the origins, expression, functions and regulation of p53-family isoforms. We conclude that despite the wealth of publications, several putative isoforms remain poorly established. Future research with improved technical approaches and the generation of isoform-specific protein detection reagents is required to establish the physiological relevance of p53-family isoforms in health and disease. In addition, our analyses suggest that p53-family variants evolved partly through convergent rather than divergent evolution from the ancestral gene.

• MeSH
• alternativní sestřih * MeSH
• lidé MeSH
• messenger RNA metabolismus   genetika   MeSH
• molekulární evoluce MeSH
• nádorový supresorový protein p53 * metabolismus   genetika   MeSH
• počátek transkripce MeSH
• protein - isoformy * genetika   metabolismus   MeSH
• regulace genové exprese MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• messenger RNA MeSH
• nádorový supresorový protein p53 * MeSH
• protein - isoformy * MeSH

The protein homologous to the tumor suppressor p53, p73, has essential roles in development and tumorigenesis. This protein exists in a wide range of isoforms with different, even antagonistic, functions. However, there are virtually no detailed morphological studies analyzing the endogenous expression of p73 isoforms at the cellular level in cancer cells. In this study, we investigated the expression and subcellular distribution of two N-terminal isoforms, TAp73 and ΔNp73, in medulloblastoma cells using immunofluorescence microscopy. Both proteins were observed in all cell lines examined, but differences were noted in their intracellular localization between the reference Daoy cell line and four newly established medulloblastoma cell lines (MBL-03, MBL-06, MBL-07 and MBL-10). In the new cell lines, TAp73 and ΔNp73 were located predominantly in cell nuclei. However, there was heterogeneity in TAp73 distribution in the cells of all MBL cell lines, with the protein located in the nucleus and also in a limited non-random area in the cytoplasm. In a small percentage of cells, we detected cytoplasmic localization of TAp73 only, i.e., nuclear exclusion was observed. Our results provide a basis for future studies on the causes and function of distinct intracellular localization of p73 protein isoforms with respect to different protein-protein interactions in medulloblastoma cells.

• MeSH
• buněčné jádro metabolismus   MeSH
• dítě MeSH
• DNA vazebné proteiny chemie   metabolismus   MeSH
• intracelulární prostor metabolismus   MeSH
• jaderné proteiny chemie   metabolismus   MeSH
• lidé MeSH
• meduloblastom metabolismus   patologie   MeSH
• nádorové buněčné linie MeSH
• nádorové supresorové proteiny chemie   metabolismus   MeSH
• předškolní dítě MeSH
• protein - isoformy metabolismus   MeSH
• protein p73 MeSH
• transport proteinů MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• delta Np73 protein, human MeSH Prohlížeč
• DNA vazebné proteiny MeSH
• jaderné proteiny MeSH
• nádorové supresorové proteiny MeSH
• protein - isoformy MeSH
• protein p73 MeSH
• TP73 protein, human MeSH Prohlížeč