TP73 is a member of the TP53 gene family and produces N- and C-terminal protein isoforms through alternative promoters, alternative translation initiation and alternative splicing. Most notably, p73 protein isoforms may either contain a p53-like transactivation domain (TAp73 isoforms) or lack this domain (ΔTAp73 isoforms) and these variants have opposing or independent functions. To date, there is a lack of well-characterised isoform-specific p73 antibodies. Here, we produced polyclonal and monoclonal antibodies to N-terminal p73 variants and the C-terminal p73α isoform, the most common variant in human tissues. These reagents show that TAp73 is a marker of multiciliated epithelial cells, while ΔTAp73 is a marker of non-proliferative basal/reserve cells in squamous epithelium. We were unable to detect ΔNp73 variant proteins, in keeping with recent data that this is a minor form in human tissues. Most cervical squamous cell carcinomas (79%) express p73α, and the distribution of staining in basal cells correlated with lower tumour grade. TAp73 was found in 17% of these tumours, with a random distribution and no association with clinicopathological features. These data indicate roles for ΔTAp73 in maintaining a non-proliferative state of undifferentiated squamous epithelial cells and for TAp73 in the production of differentiated multiciliated cells.

• Klíčová slova
• Cervical cancer, Endometrium, Fallopian tube, Multiciliated cells, Squamous epithelial stem cells, p73 isoforms,
• MeSH
• epitelové buňky metabolismus   MeSH
• lidé MeSH
• monoklonální protilátky MeSH
• nádorové buněčné linie MeSH
• nádory děložního čípku metabolismus   patologie   genetika   MeSH
• nádory metabolismus   patologie   genetika   MeSH
• protein - isoformy * metabolismus   genetika   MeSH
• protein p73 * metabolismus   genetika   MeSH
• spinocelulární karcinom metabolismus   patologie   genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• delta Np73 protein, human MeSH Prohlížeč
• monoklonální protilátky MeSH
• protein - isoformy * MeSH
• protein p73 * MeSH
• TP73 protein, human MeSH Prohlížeč

p73, a member of the p53 family, exhibits activities similar to those of p53, including the ability to induce growth arrest and apoptosis. p73 influences chemotherapeutic responses in human cancer patients, in association with p53. Alternative splicing of the TP73 gene produces many p73 C- and N-terminal isoforms, which vary in their transcriptional activity towards p53-responsive promoters. In this paper, we show that the C-terminal spliced isoforms of the p73 protein differ in their DNA-binding capacity, but this is not an accurate predictor of transcriptional activity. In different p53-null cell lines, p73beta induces either mitochondrial-associated or death receptor-mediated apoptosis, and these differences are reflected in different gene expression profiles. In addition, p73 induces cell cycle arrest and p21(WAF1) expression in H1299 cells, but not in Saos-2. This data shows that TAp73 isoforms act differently depending on the tumour cell background, and have important implications for p73-mediated therapeutic responses in individual human cancer patients.

• MeSH
• aktivace transkripce MeSH
• alternativní sestřih MeSH
• apoptóza fyziologie   MeSH
• buněčné linie MeSH
• buněčný cyklus fyziologie   MeSH
• DNA vazebné proteiny genetika   metabolismus   MeSH
• genetická transkripce MeSH
• jaderné proteiny genetika   metabolismus   MeSH
• lidé MeSH
• nádorové supresorové proteiny genetika   metabolismus   MeSH
• nádorový supresorový protein p53 genetika   metabolismus   MeSH
• protein - isoformy genetika   metabolismus   MeSH
• protein p73 MeSH
• sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
• signální transdukce fyziologie   MeSH
• stanovení celkové genové exprese MeSH
• trans-aktivátory genetika   metabolismus   MeSH
• transkripční faktory MeSH
• vazba proteinů MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA vazebné proteiny MeSH
• jaderné proteiny MeSH
• nádorové supresorové proteiny MeSH
• nádorový supresorový protein p53 MeSH
• protein - isoformy MeSH
• protein p73 MeSH
• TP53 protein, human MeSH Prohlížeč
• TP63 protein, human MeSH Prohlížeč
• TP73 protein, human MeSH Prohlížeč
• trans-aktivátory MeSH
• transkripční faktory MeSH