Most cited article - PubMed ID 20803057
Analysis of the intracellular localization of p73 N-terminal protein isoforms TAp73 and ∆Np73 in medulloblastoma cell lines
The p73 protein is a member of the p53 family, and this protein is known to be essential for the maintenance of genomic stability, DNA repair, and apoptosis regulation. Transcription from two promoters leads to two main N-terminal isoforms: the TAp73 isoform is reported to have tumor suppressor function, whereas the ΔNp73 isoform likely has oncogenic potential. The present study is focused on the investigation of a possible role of both these p73 N-terminal isoforms in the process of centrosome amplification. HGG-02 and GM7 glioblastoma cell lines and the Daoy medulloblastoma cell line were used in this study. The cells were analyzed using indirect immunofluorescence to determine TAp73 and ΔNp73 expression patterns and possible co-localization with the BubR1 protein, as well as the number of centrosomes. A transiently transfected GM7 cell line was used to verify the results concerning the N-terminal isoforms in relation to centrosome amplification. We found that increased immunoreactivity for the ΔNp73 isoform is associated with the occurrence of an abnormal number of centrosomes in particular cells. Using the transiently transfected GM7 cell line, we confirmed that centrosome amplification is present in cells with overexpression of the ΔNp73 isoform. In contrast, the immunoreactivity for the TAp73 isoform was weak or medium in most of the cells with an aberrant number of centrosomes. To determine the putative counterpart of the p73 N-terminal isoforms among spindle assembly checkpoint (SAC) proteins, we also evaluated possible interactions between the N-terminal isoforms and BubR1 protein, but no co-localization of these proteins was observed.
- Keywords
- BubR1, Centrosome amplification, Glioblastoma multiforme, Medulloblastoma, TAp73, ΔNp73,
- MeSH
- Gene Amplification * MeSH
- Centrosome physiology MeSH
- Chromosome Aberrations * MeSH
- DNA-Binding Proteins genetics MeSH
- Fluorescent Antibody Technique, Indirect MeSH
- Nuclear Proteins genetics MeSH
- Humans MeSH
- Tumor Cells, Cultured MeSH
- Tumor Suppressor Proteins genetics MeSH
- Brain Neoplasms genetics pathology MeSH
- DNA Repair MeSH
- Promoter Regions, Genetic MeSH
- Protein Isoforms MeSH
- Tumor Protein p73 MeSH
- Protein Serine-Threonine Kinases genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- BUB1 protein, human MeSH Browser
- delta Np73 protein, human MeSH Browser
- DNA-Binding Proteins MeSH
- Nuclear Proteins MeSH
- Tumor Suppressor Proteins MeSH
- Protein Isoforms MeSH
- Tumor Protein p73 MeSH
- Protein Serine-Threonine Kinases MeSH
- TP73 protein, human MeSH Browser