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Genes & Dev. 14 (6): 704-718

Copyright © 2000 by Cold Spring Harbor Laboratory Press.

Vol. 14, No. 6, pp. 704-718, March 15, 2000

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

Laura D. Attardi,1 Elizabeth E. Reczek,1 Corinna Cosmas,1 Elizabeth G. Demicco,1 Mila E. McCurrach,2 Scott W. Lowe,2 and Tyler Jacks1,3,4

1 Department of Biology and Center for Cancer Research, and 3 Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 USA; 2 Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724 USA

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 G1 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 G1-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.

[Key Words: p53; apoptosis; PERP; MEFs; PMP-22/gas3]

4 Corresponding author.

GENES & DEVELOPMENT 14:704-718 © 2000 by Cold Spring Harbor Laboratory Press  ISSN 0890-9369/00 $5.00

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