Cited by 64Cell death mechanisms and regulationCancer-related Molecular PathwaysMicroRNA in disease regulation

Loss of programmed cell death 4 induces apoptosis by promoting the translation of procaspase-3 mRNA

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Eto, K, Goto, S, Nakashima, W, Ura, Y, Abe, S-I·2012·Cell Death & Differentiation

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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Crossref · 10.1038/cdd.2011.126

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  • Loss of PDCD4 up-regulates pro-caspase 3 expression resulting in elevation of active caspase 3 levels and induction of apoptosis without apoptotic stimuli in HeLa cells.

    “Eto et al. demonstrated that the loss of PDCD4 up-regulated pro-caspase 3 expression resulting in the elevation of active caspase 3 levels and the induction of apoptosis without apoptotic stimuli in HeLa cells [43].”
  • PDCD4 specific siRNA induces tumor cell death.

    “PDCD4 specific siRNA also induces tumor cell death [43,44].”

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  1. Matsuhashi S, Yoshinaga H, Yatsuki H, Tsugita A, Hori K. Isolation of a novel gene from a human cell line with Pr-28mAb which recognizes a nuclear antigen involved in the cell cycle. Res Commun Biochem Cell Mol Biol. 1997;1:109–120. [Google Scholar]

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Authors
Eto, K., Goto, S., Nakashima, W., Ura, Y., & Abe, S.-I.
Affiliations
Kumamoto University (JP)
Corresponding author
Eto, K
ORCID
Eto, K
Venue
Cell Death & Differentiation
Published
2011-09-30
Volume
19
Issue
4
Pages
573-581
ISSN
  • 1350-9047 (ISSN-L)
  • 1476-5403
OpenAlex
W1967600311
Cited by
64
References
36
Citations by year
2026: 1 · 2025: 2 · 2024: 3 · 2023: 7 · 2022: 5 · 2021: 6 · 2020: 2 · 2019: 6 · 2018: 7 · 2017: 4 · 2016: 1 · 2015: 2 · 2014: 10 · 2013: 6 · 2012: 2
FWCI
2.34
Type
journal article
Language
en
Open access
Locations
  • Cell Death and Differentiation (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Japan Society for the Promotion of Science (22247008)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
Keywords
PDCD4, apoptosis, procaspase-3, mRNA translation, protein synthesis inhibition, microRNA, caspase-3 activation, PARP cleavage, tumor suppression, RNA interference
MeSH terms
HeLa Cells, Humans, RNA, Messenger, Protein Biosynthesis, Gene Expression Regulation, Enzymologic, RNA-Binding Proteins, Apoptosis, Apoptosis Regulatory Proteins, Caspase 3

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