The DOI matches its Crossref record; 21 of the 22 references it cites were found in a registry or an index, and 1 are not checked yet.
PDCD4 inhibits translation initiation by binding to eIF4A using both its MA3 domains
Open accessAbstract
Programmed Cell Death 4 (PDCD4) is a protein known to bind eukaryotic initiation factor 4A (eIF4A), inhibit translation initiation, and act as a tumor suppressor. PDCD4 contains two C-terminal MA3 domains, which are thought to be responsible for its inhibitory function. Here, we analyze the structures and inhibitory functions of these two PDCD4 MA3 domains by x-ray crystallography, NMR, and surface plasmon resonance. We show that both MA3 domains are structurally and functionally very similar and bind specifically to the eIF4A N-terminal domain (eIF4A-NTD) using similar binding interfaces. We found that the PDCD4 MA3 domains compete with the eIF4G MA3 domain and RNA for eIF4A binding. Our data provide evidence that PDCD4 inhibits translation initiation by displacing eIF4G and RNA from eIF4A. The PDCD4 MA3 domains act synergistically to form a tighter and more stable complex with eIF4A, which explains the need for two tandem MA3 domains.
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“Fourth, levels of the translation repressor PDCD4 (refs. 36,37) were significantly reduced in Tex cells both in vitro and in vivo”
From Proteotoxic stress response drives T cell exhaustion and immune evasion (2025) · cites this paper as [36]
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“MA-3 domains of PDCD4 are homologous to the MA-3 domain of eIF4G and compete with it for eIF4A binding39,40.”
From PDCD4 triggers α-synuclein accumulation and motor deficits via co-suppressing TFE3 and TFEB translation in a model of Parkinson’s disease (2024) · cites this paper as [39]
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Cites
S6K1- and ßTRCP-Mediated Degradation of PDCD4 Promotes Protein Translation and Cell Growth
Dorrello, N. V., Peschiaroli, A., Guardavaccaro, D., Colburn, N. H., Sherman, N. E., & Pagano, M. (2006) · Science · doi:10.1126/science.1130276 · Cited by 731
Bidirectional RNA Helicase Activity of Eucaryotic Translation Initiation Factors 4A and 4F
Rozen, F., Edery, I., Meerovitch, K., Dever, T. E., Merrick, W. C., & Sonenberg, N. (1990) · Molecular and Cellular Biology · doi:10.1128/mcb.10.3.1134 · Cited by 632
Mutational analysis of a DEAD box RNA helicase: the mammalian translation initiation factor eIF‐4A.
Pause, A., & Sonenberg, N. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05330.x · Cited by 615
Yang, H.-S., Jansen, A. P., Komar, A. A., Zheng, X., Merrick, W. C., Costes, S., Lockett, S. J., Sonenberg, N., & Colburn, N. H. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.1.26-37.2003 · Cited by 494
Imataka, H., & Sonenberg, N. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.12.6940 · Cited by 292
NMR spectroscopy: a multifaceted approach to macromolecular structure
Ferentz, A. E., & Wagner, G. (2000) · Quarterly Reviews of Biophysics · doi:10.1017/s0033583500003589 · Cited by 239
Self-citationBidirectional RNA Helicase Activity of Eucaryotic Translation Initiation Factors 4A and 4F
Rozen, F., Edery, I., Meerovitch, K., et al. (1990) · Molecular and Cellular Biology · doi:10.1128/mcb.10.3.1134-1144.1990 · Cited by 225
Translation initiation: structures, mechanisms and evolution
Marintchev, A., & Wagner, G. (2004) · Quarterly Reviews of Biophysics · doi:10.1017/s0033583505004026 · Cited by 223
Self-citationIsolation of a novel mouse gene MA-3 that is induced upon programmed cell death
Shibahara, K., Asano, M., Ishida, Y., Aoki, T., Koike, T., & Honjo, T. (1995) · Gene · doi:10.1016/0378-1119(95)00607-9 · Cited by 223
Morino, S., Imataka, H., Svitkin, Y. V., Pestova, T. V., & Sonenberg, N. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.2.468-477.2000 · Cited by 206
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From unwinding to clamping — the DEAD box RNA helicase family
Linder, P., & Jankowsky, E. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3154 · Cited by 1,177
miR‐21: a small multi‐faceted RNA
Krichevsky, A. M., & Gabriely, G. (2009) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2008.00556.x · Cited by 987
Targeting the eIF4F Translation Initiation Complex: A Critical Nexus for Cancer Development
Pelletier, J., Graff, J., Ruggero, D., & Sonenberg, N. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-2789 · Cited by 367
Bourguignon, L., Spevak, C. C., Wong, G., Xia, W., & Gilad, E. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.027466 · Cited by 318
The tumour suppressor Pdcd4: recent advances in the elucidation of function and regulation
Lankat–Buttgereit, B., & Göke, R. (2009) · Biology of the Cell · doi:10.1042/bc20080191 · Cited by 315
Metadata
- Authors
- Suzuki, C., Garces, R. G., Edmonds, K. A., Hiller, S., Hyberts, S. G., Marintchev, A., & Wagner, G.
- Affiliations
- Harvard University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2008-03-04
- Volume
- 105
- Issue
- 9
- Pages
- 3274-3279
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2265113
- OpenAlex
- W2079859240
- Cited by
- 165
- References
- 21
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 15 · 2023: 5 · 2022: 4 · 2021: 8 · 2020: 10 · 2019: 8 · 2018: 5 · 2017: 5 · 2016: 4 · 2015: 9 · 2014: 15 · 2013: 14 · 2012: 12
- FWCI
- 4.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Energy (DE‐ AC02‐06CH11357, AC02‐06CH11357, contract DE-AC02-06CH11357, 06CH11357, RR-15301, DE-AC02-)
- National Institutes of Health (DE-AC02–06CH11357, GM47467, RR15301)
- National Cancer Institute (DE-AC02-06CH11357, CA68262, K01CA119107, R01CA068262)
- National Institute of General Medical Sciences (GM47467, P01GM047467)
- National Center for Research Resources (RR 15301, P41RR015301)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- PDCD4, eIF4A, translation initiation inhibition, eIF4G, protein-protein binding, tumor suppressor, protein complex stability
- MeSH terms
- Binding, Competitive, Humans, Protein Binding, RNA, Protein Biosynthesis, RNA-Binding Proteins, Protein Structure, Tertiary, Crystallography, X-Ray, Eukaryotic Initiation Factor-4A, Eukaryotic Initiation Factor-4G, Apoptosis Regulatory Proteins
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