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Updated: Mar 15, 2026
Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
p63 is required beside p53 for PERP-mediated apoptosis in uveal melanoma
Raheela Awais1, David G Spiller2, Michael R H White2
1Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, William Henry Duncan Building, 6 West Derby Street, Liverpool L7 8TX, UK.
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.
Insights
p63 expression is crucial for initiating apoptosis in uveal melanoma (UM) by enabling PERP (p53 apoptosis effector related to PMP-22) activation. Its absence impairs p53-mediated apoptosis, highlighting p63
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- PERP (p53 apoptosis effector related to PMP-22) is a p53 target gene, but its expression and apoptotic function are impaired in uveal melanoma (UM).
- Chromosome 3 alterations, including those affecting p63, are characteristic of high-risk UM and p63 can activate PERP.
- Understanding the role of p63 in PERP-mediated apoptosis is critical for UM research.
Purpose of the Study:
- To investigate the functional role of p63 expression in initiating p53/PERP-mediated apoptosis in UM.
- To determine if p63 expression is necessary for PERP induction and subsequent apoptosis in UM cell lines.
Main Methods:
- Quantitative PCR (qPCR) and immunoblotting were used to monitor PERP expression in UM cell lines.
- Transient expression of p63-turbo GFP (p63-tGFP) was performed in apoptosis-resistant, 3q-deficient OCM-1 cells.
- Expression, localization, and apoptosis induction were analyzed using qPCR, immunoblotting, and confocal microscopy.
Main Results:
- PERP was significantly downregulated in all tested UM cell lines.
- DNA-damaging agents failed to induce apoptosis or activate PERP in OCM-1 cells lacking functional p63.
- p63-tGFP expression restored apoptosis and significantly increased PERP expression and p53 accumulation.
Conclusions:
- Reduced PERP levels and impaired p53-mediated apoptosis in UM are linked to a lack of p63.
- p63 expression is essential for PERP-mediated apoptosis in the context of uveal melanoma.
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