Loss of Programmed Cell Death 4 Induces Apoptosis by Promoting the Translation of Procaspase-3 MRNA

Overview

Journal Cell Death Differ

Specialty Cell Biology

Date 2011 Oct 1

PMID 21959934

Citations 33

Authors

K Eto

S Goto

W Nakashima

Y Ura

S-I Abe

Affiliations

Soon will be listed here.

Abstract

The programmed cell death 4 (Pdcd4), a translation inhibitor, plays an essential role in tumor suppression, but its role in apoptosis remains unclear. Here we show that Pdcd4 is a critical suppressor of apoptosis by inhibiting the translation of procaspase-3 mRNA. Pdcd4 protein decreased more rapidly through microRNA-mediated translational repression following apoptotic stimuli than did the activation of procaspase-3, cleavage of poly(ADP)ribose polymerase (PARP) by active caspase-3, and nuclear fragmentation. Strikingly, the loss of Pdcd4 by the specific RNA interference increased procaspase-3 expression, leading to its activation and PARP cleavage even without apoptotic stimuli, and sensitized the cells to apoptosis. Thus, our findings provide insight into a novel mechanism for Pdcd4 as a regulator of apoptosis.

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