IntroductionCell death by apoptosis is critical for the health of multi-cellular organisms being involved both in the development and in the maintenance of tissue homeostasis, as well as in the elimination of abnormal cells [1]. The transcription factor p53 is part of a complex signalling network involved in the regulation of cellular responses to oncogenic stress, including DNA damage, which performs its tumour suppression role by either inducing cell cycle arrest (in G1 and/or G2) or eliminating abnormal cells by apoptosis [2][3][4]. The function of p53 as a tumour suppressor is underlined by the presence of its mutations in approximately half of human cancers [5], whereas the p53 pathway is compromised by other means in the majority of other cancers [3,6]. The mechanism by which p53 activates cell cycle arrest is far better characterized [7][8][9]
Abstract p53 apoptosis effector related to PMP-22 (PERP) is a transcriptional target gene of p53 tumour suppressor that is specifically induced during apoptosis and not during cell cycle arrest. In primary uveal melanoma (UM), the most common intraocular malignancy in adults that has a reportedly unaffected signalling pathway upstream of and including p53, PERP expression is down-regulated in the metastatic monosomy 3-type tumours, compared with the less aggressive disomy 3-type tumours. Here, we demonstrate experimentally, by the use of full-length PERP-green fluorescent protein (GFP) fusions and real-time confocal microscopy, the intracellular targeting and plasma membrane localization of PERP in living UM cells and show that expression of PERP induces caspase-mediated apoptosis in UM cells. Induction of PERP expression in GFP-PERP-transfected UM cells leads to increased levels of cleaved caspase-8 forms, as well as to reduction of its full