In:
Genes & Development, Cold Spring Harbor Laboratory, Vol. 14, No. 6 ( 2000-03-15), p. 704-718
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 p53-dependent apoptosis.
Type of Medium:
Online Resource
ISSN:
0890-9369
,
1549-5477
DOI:
10.1101/gad.14.6.704
Language:
English
Publisher:
Cold Spring Harbor Laboratory
Publication Date:
2000
detail.hit.zdb_id:
1467414-2
SSG:
12
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