p63 is required beside p53 for PERP-mediated apoptosis in uveal melanoma
| Autor: | Awais, Raheela, Spiller, David G, White, Michael R H, Paraoan, Luminita |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Transcriptional Activation
Uveal Neoplasms p53 Ultraviolet Rays Recombinant Fusion Proteins Immunoblotting monosomy 3 PERP Real-Time Polymerase Chain Reaction TNF-Related Apoptosis-Inducing Ligand Cell Line Tumor Humans chromosome 3 Molecular Diagnostics Melanoma p63 Microscopy Confocal integumentary system Tumor Suppressor Proteins apoptosis Gene Expression Regulation Neoplastic stomatognathic diseases sense organs uveal melanoma DNA Damage Transcription Factors |
| Zdroj: | British Journal of Cancer Awais, R, Spiller, D G, White, M R H & Paraoan, L 2016, ' p63 is required beside p53 for PERP-mediated apoptosis in uveal melanoma ', British Journal of Cancer, vol. 115, no. 8, pp. 983-992 . https://doi.org/10.1038/bjc.2016.269 |
| DOI: | 10.1038/bjc.2016.269 |
| Popis: | Background: PERP (p53 apoptosis effector related to PMP-22), a transcriptional target of p53, is downregulated and contributes to the impairment of apoptosis in uveal melanoma (UM). Intriguingly, PERP is not induced in UM despite functional p53. p63, located on chromosome 3, which is characteristically altered in high-risk UM, can transactivate PERP. Here, we determine the functional role of p63 expression in the initiation of p53/PERP-mediated apoptosis in UM. Methods: PERP expression was monitored by quantitative PCR (qPCR) and immunoblotting in UM cell lines treated with DNA-damaging agents. The functional role of p63 was assessed by transient expression of p63-turbo GFP (p63-tGFP) in the apoptosis- resistant, 3q-deficient OCM-1 cells. Expression and localisation of p63, PERP and p53, and induction of apoptosis were characterised by qPCR, immunoblotting and live cell confocal microscopy. Results: PERP expression was significantly downregulated in all UM cell lines. DNA-damaging treatments failed to induce apoptosis and activate PERP in OCM-1 cells, which displayed non-functional levels of p63. Expression of p63-tGFP induced apoptosis with marked increase in PERP expression and associated p53 accumulation. Conclusions: Lack of p63 contributes to reduced PERP levels and impaired p53-mediated apoptosis in UM. p63 expression is required for PERP-mediated apoptosis in UM. |
| Databáze: | OpenAIRE |
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