Loss of programmed cell death 4 induces apoptosis by promoting the translation of procaspase-3 mRNA
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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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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].”
From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [43]
PDCD4 specific siRNA induces tumor cell death.
“PDCD4 specific siRNA also induces tumor cell death [43,44].”
From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [43]
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Eto, K., & Suemoto, T. (2023) · Experimental Cell Research · doi:10.1016/j.yexcr.2023.113713 · Cited by 1 · see citing works
Self-citationNovel strategy for treating neurotropic viral infections using hypolipidemic drug AtorvastatinPreprint
Mallick, S., Chakraborty, S., Hazra, B., Dev, S., Mukherjee, S., Wani, M. A., & Basu, A. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/639096 · Cited by 2 · see citing works
Role of PDCD4 in inflammation and tumors: a double-edged sword
Jia, Y., Chen, X., & Zhang, L. (2018) · Scientia Sinica Vitae · doi:10.1360/n052018-00164
Tian, B., Li, X., huang, X., & Liu, W. (2021) · Research Square · doi:10.21203/rs.3.rs-757501/v1
Liu, W., Tan, X., Huang, X., & Tian, B. (2024) · Journal of Biomedical Nanotechnology · doi:10.1166/jbn.2024.3834
Wang, T., Yang, X., Lee, Y., Song, J. H., Childs‐Disney, J. L., Garcia, J. G. N., & Disney, M. D. (2026) · ACS Chemical Biology · doi:10.1021/acschembio.5c00979
- 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
- PMC
- PMC3307972
- 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
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- 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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