PERP-ing into diverse mechanisms of cancer pathogenesis: Regulation and role of the p53/p63 effector PERP

Roberts, Owain and Paraoan, Luminita ORCID: 0000-0001-7568-7116 (2020) PERP-ing into diverse mechanisms of cancer pathogenesis: Regulation and role of the p53/p63 effector PERP. BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 1874 (1). 188393-.

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Official URL: http://dx.doi.org/10.1016/j.bbcan.2020.188393

Abstract

The tetraspan plasma membrane protein PERP (p53 apoptosis effector related to PMP22) is a lesser-known transcriptional target of p53 and p63. A member of the PMP22/GAS3/EMP membrane protein family, PERP was originally identified as a p53 target specifically trans-activated during apoptosis, but not during cell-cycle arrest. Several studies have since shown downregulation of PERP expression in numerous cancers, suggesting that PERP is a tumour suppressor protein. This review focusses on the important advances made in elucidating the mechanisms regulating PERP expression and its function as a tumour suppressor in diverse human cancers, including breast cancer and squamous cell carcinoma. Investigating PERP's role in clinically-aggressive uveal melanoma has revealed that PERP engages a positive-feedback loop with p53 to regulate its own expression, and that p63 is required beside p53 to achieve pro-apoptotic levels of PERP in this cancer. Furthermore, the recent discovery of the apoptosis-mediating interaction of PERP with SERCA2b at the plasma membrane-endoplasmic reticulum interface demonstrates a novel mechanism of PERP stabilisation, and how PERP can mediate Ca<sup>2+</sup> signalling to facilitate apoptosis. The multi-faceted role of PERP in cancer, involving well-documented functions in mediating apoptosis and cell-cell adhesion is discussed, alongside PERP's emerging roles in epithelial-mesenchymal transition, and PERP crosstalk with inflammation signalling pathways, and other signalling pathways. The potential for restoring PERP expression as a means of cancer therapy is also considered.

Item Type:	Article
Uncontrolled Keywords:	PERP, Apoptosis, Adhesion, Inflammation, p53/p63, Cancer
Depositing User:	Symplectic Admin
Date Deposited:	10 Aug 2020 08:24
Last Modified:	18 Jan 2023 23:38
DOI:	10.1016/j.bbcan.2020.188393
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3096688