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Beschreibung

Tumor protein 63 (UniProt: Q9H3D4, also known as p63, Chronic ulcerative stomatitis protein, CUSP, Keratinocyte transcription factor KET, Transformation-related protein 63, TP63, Tumor protein p73-like, p73L, P40, P51) is encoded by the TP63 (also known as KET, P63, P73H, P73L, TP73L) gene (Gene ID: 8626) in human. TP63 is a member of the p53 protein family that is widely expressed. TP63 acts as a sequence specific DNA binding transcriptional activator or repressor. TP63 is shown to bind to DNA as a homotetramer and its DNA binding region is localized to amino acids 170-362. It has a transcription activation region (aa 1-107) and a transactivation inhibition region (aa 610-680), which can interact with, and inhibit the activity of the N-terminal transcriptional activation domain of TA-type isoforms. Twelve different isoforms of TP63 have been described that are produced by alternative promoter usage and alternative splicing. These isoforms contain a varying set of transactivation and auto-regulating transactivation inhibiting domains thus showing an isoform specific activity. The ratio of DeltaN-type and TA-type isoforms governs the maintenance of epithelial stem cell compartments and regulates the initiation of epithelial stratification from the undifferentiated embryonal ectoderm. Isoform 2 is reported to activate RIPK4 transcription and may be required in conjunction with TP73/p73 for initiation of p53/TP53 dependent apoptosis in response to genotoxic insults and the presence of activated oncogenes. Isoform 10 is predominantly expressed in skin squamous cell carcinoma, but not in normal skin tissue.