Editors' ChoiceApoptosis

A p53-dependent Apoptosis Perpetrator

Science's STKE  04 Apr 2000:
Vol. 2000, Issue 26, pp. tw1
DOI: 10.1126/stke.2000.26.tw1

The activation of p53 can lead to cell-cycle arrest or apoptosis. Attardi et al. used subtractive hybridization to identify genes involved in the p53-dependent apoptosis pathway. They identified a gene called p53 apoptosis effector related to PMP-22 (PERP) that is expressed in p53-mediated apoptosis of mouse embryonic fibroblasts (MEFs), but not expressed in p53-deficient MEFs. Transfection of luciferase vectors containing the PERP promoter into wild-type and p53-deficient MEFs revealed that the PERP promoter was activated in a p53-dependent manner, through p53 response elements. Fluorescence assays indicated that PERP localizes to the Golgi complex and, to a lesser extent, the plasma membrane. In the absence of p53, overexpression of PERP led to apoptosis of MEFs. Expression of Bcl-2 inhibited apoptosis induced by overexpressed PERP without affecting the amount of PERP expressed. Thus, p53-induced expression of PERP may be sufficient to cause apoptosis. PERP shares sequence similarity to the PMP-22/gas3 family of tetraspanins, a group of plasma membrane proteins whose mutations are thought to lead to human neuropathies such as Charcot-Marie-Tooth.

Attardi, L.D., Reczek, E.E., Cosmas, C., Demicco, E.G., McCurrach, M.E., Lowe, S.W., and Jacks, T. (2000) PERP, an apoptosis-associated target of p53, is a novel member of the PMP-22/gas3 family. Genes Dev. 14: 704 -718. [Abstract] [Full Text]