PERP, an apoptosis-associated target of p53, is a novel member of the PMP-22/gas3 family

Attardi, L. D., Reczek, E. E., Cosmas, C., Demicco, E. G., McCurrach, M. E., Lowe, S. W., Jacks, T. (March 2000) PERP, an apoptosis-associated target of p53, is a novel member of the PMP-22/gas3 family. Genes & Development, 14 (6). pp. 704-718. ISSN 0890-9369

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URL: http://www.ncbi.nlm.nih.gov/pubmed/10733530
DOI: 10.1101/gad.14.6.704

Abstract

The p53 tumor suppressor activates either cell cycle arrest or apoptosis in response to cellular stress. Mouse embryo fibroblasts (MEFs) provide a powerful primary cell system to study both p53-dependent pathways. Specifically, in response to DNA damage, MEFs undergo p53-dependent G(1) arrest, whereas MEFs expressing the adenovirus E1A oncoprotein undergo p53-dependent apoptosis. As the p53-dependent apoptosis pathway is not well understood, we sought to identify apoptosis-specific p53 target genes using a subtractive cloning strategy. Here, we describe the characterization of a gene identified in this screen, PERP, which is expressed in a p53-dependent manner and at high levels in apoptotic cells compared with G(1)-arrested cells. PERP induction is linked to p53-dependent apoptosis, including in response to E2F-1-driven hyperproliferation. Furthermore, analysis of the PERP promoter suggests that PERP is directly activated by p53. PERP shows sequence similarity to the PMP-22/gas3 tetraspan membrane protein implicated in hereditary human neuropathies such as Charcot-Marie-Tooth, Like PMP-22/gas3, PERP is a plasma membrane protein, and importantly, its expression causes cell death in fibroblasts. Taken together, these data suggest that PERP is a novel effector of p59-dependent apoptosis.

Item Type: Paper
Uncontrolled Keywords: p53 apoptosis PERP MEFs PMP-22/gas3 CELL-CYCLE ARREST WILD-TYPE P53 P53-DEPENDENT APOPTOSIS TUMOR-SUPPRESSOR GROWTH ARREST IN-VIVO TRANSCRIPTIONAL ACTIVATION REGULATED EXPRESSION MEDIATED APOPTOSIS MYELIN PROTEIN
Subjects: organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > apoptosis
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > p53
CSHL Authors:
Communities: CSHL labs > Lowe lab
Depositing User: Matt Covey
Date: March 2000
Date Deposited: 29 Jan 2014 19:34
Last Modified: 29 Jan 2014 19:34
PMCID: PMC316461
Related URLs:
URI: https://repository.cshl.edu/id/eprint/29428

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