The unique evolution of the programmed cell death 4 protein in plants
Open accessAbstract
Background: The programmed cell death 4 (PDCD4) protein is induced in animals during apoptosis and functions to inhibit translation and tumor promoter-induced neoplastic transformation. PDCD4 is composed of two MA3 domains that share similarity with the single MA3 domain present in the eukaryotic translation initiation factor (eIF) 4G, which serves as a scaffold protein to assemble several initiation factors needed for the recruitment of the 40S ribosomal subunit to an mRNA. Although eIF4A is an ATP-dependent RNA helicase that binds the MA3 domain of eIF4G to promote translation initiation, binding of eIF4A to the MA3 domains of PDCD4 inhibits protein synthesis. Genes encoding PDCD4 are present in many lower eukaryotes and in plants, but PDCD4 in higher plants is unique in that it contains four MA3 domains and has been implicated in ethylene signaling and abiotic stress responses. Here, we examine the evolution of PDCD4 in plants. Results: In older algal lineages, PDCD4 contains two MA3 domains similar to the homolog in animals. By the appearance of early land plants, however, PDCD4 is composed of four MA3 domains which likely is the result of a duplication of the two MA3 domain form of the protein. Evidence from fresh water algae, from which land plants evolved, suggests that the duplication event occurred prior to the colonization of land. PDCD4 in more recently evolved chlorophytes also contains four MA3 domains but this may have resulted from an independent duplication event. Expansion and divergence of the PDCD4 gene family occurred during land plant evolution with the appearance of a distinct gene member following the evolution of basal angiosperms. Conclusions: The appearance of a unique form of PDCD4 in plants correlates with the appearance of components of the ethylene signaling pathway, suggesting that it may represent the adaptation of an existing protein involved in programmed cell death to one that functions in abiotic stress responses through hormone signaling.
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The PDCD4 gene homolog is present in plants but not in yeasts.
“The gene homolog is present in plants but not in yeasts [16].”
From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [16]
The Background states that PDCD4 homologs are present in plants, but says only that none has been reported in yeast. The claim turns that qualified observation into a categorical assertion that the homolog is absent from yeasts. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe PDCD4 gene is well conserved in species; human and fish (elephant shark) protein sequences are 72% identical.
“The gene is well conserved in species; for example, the homology between human and fish (elephant shark) is 72 % identical in the protein level.”
From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [16]
The Results section ('The four MA3 domain PDCD4 protein is unique to plants'; page unavailable) reports considerable conservation among angiosperm PDCD4 proteins and identifies homologs in animals. It does not report a human–elephant shark comparison or 72% protein-sequence identity (searched: 'elephant shark' and '72%'). (LLM, conf=0.85)
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Cites
Guindon, S., Dufayard, J.-F., Lefort, V., Anisimova, M., Hordijk, W., & Gascuel, O. (2010) · Systematic Biology · doi:10.1093/sysbio/syq010 · Cited by 18,376 · see citing works
Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega
Sievers, F., Wilm, A., Dineen, D., Gibson, T., Karplus, K., Li, W.-Z., Lopez, R., McWilliam, H., Remmert, M., Söding, J., et al. (2011) · Molecular Systems Biology · doi:10.1038/msb.2011.75 · Cited by 15,576 · see citing works
ExPASy: the proteomics server for in-depth protein knowledge and analysis
Gasteiger, E. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg563 · Cited by 5,602 · see citing works
Phytozome: a comparative platform for green plant genomics
Goodstein, D. M., Shu, S., Howson, R. W., Neupane, R., Hayes, R. D., Fazo, J., Mitros, T., Dirks, W., Hellsten, U., Putnam, N. H., et al. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr944 · Cited by 5,448 · see citing works
An Improved General Amino Acid Replacement Matrix
Le, S. Q., & Gascuel, O. (2008) · Molecular Biology and Evolution · doi:10.1093/molbev/msn067 · Cited by 3,127 · see citing works
The Norway spruce genome sequence and conifer genome evolution
Nystedt, B., Street, N. R., Wetterbom, A., Zuccolo, A., Lin, Y., Scofield, D. G., Vezzi, F., Delhomme, N., Giacomello, S., Alexeyenko, A., et al. (2013) · Nature · doi:10.1038/nature12211 · Cited by 1,463 · see citing works
Circularization of mRNA by Eukaryotic Translation Initiation Factors
Wells, S. E., Hillner, P. E., Vale, R. D., & Sachs, A. B. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80122-7 · Cited by 968 · see citing works
Translational control in biology and medicine
Mathews, M. B., Sonenberg, N., & Hershey, J. W. B. (2007) · Cited by 661 · see citing works
Human eukaryotic translation initiation factor 4G (eIF4G) recruits Mnk1 to phosphorylate eIF4E
Pyronnet, S., Imataka, H., Gingras, A., Fukunaga, R., Hunter, T., & Sonenberg, N. (1999) · The EMBO Journal · doi:10.1093/emboj/18.1.270 · Cited by 639 · see citing works
The Molecular Mechanics of Eukaryotic Translation
Kapp, L. D., & Lorsch, J. R. (2004) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.73.030403.080419 · Cited by 540 · see citing works
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 · see citing works
A common function for mRNA 5' and 3' ends in translation initiation in yeast.Preprint
Tarun, S. Z., & Sachs, A. B. (1995) · Genes & Development · doi:10.1101/gad.9.23.2997 · Cited by 374 · see citing works
Modulation of the Helicase Activity of eIF4A by eIF4B, eIF4H, and eIF4F
Rogers, G. W., Richter, N. J., Lima, W. F., & Merrick, W. C. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m100157200 · Cited by 339 · see citing works
Differentially expressed protein Pdcd4 inhibits tumor promoter-induced neoplastic transformation
Cmarik, J. L., Min, H., Hegamyer, G., Zhan, S., Kulesz-Martin, M., Yoshinaga, H., Matsuhashi, S., & Colburn, N. H. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.24.14037 · Cited by 254 · see citing works
The plant translational apparatus
Browning, K. S. (1996) · Plant Molecular Biology · doi:10.1007/bf00039380 · Cited by 224 · see citing works
Isolation 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 · see citing works
A Conserved HEAT Domain within eIF4G Directs Assembly of the Translation Initiation Machinery
Marcotrigiano, J., Lomakin, I. B., Sonenberg, N., Pestova, T. V., Hellen, C. U. T., & Burley, S. K. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00167-8 · Cited by 216 · see citing works
Starting the protein synthesis machine: eukaryotic translation initiation
Preiss, T., & W. Hentze, M. (2003) · BioEssays · doi:10.1002/bies.10362 · Cited by 216 · see citing works
Ethylene perception and signaling: an evolutionary perspective
Bleecker, A. B. (1999) · Trends in Plant Science · doi:10.1016/s1360-1385(99)01427-2 · Cited by 216 · see citing works
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 · see citing works
Yang, H.-S., Cho, M.-H., Zakowicz, H., Hegamyer, G., Sonenberg, N., & Colburn, N. H. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.9.3894-3906.2004 · Cited by 199 · see citing works
Wang, W., Esch, J. J., Shiu, S., Agula, H., Binder, B. M., Chang, C., Patterson, S. E., & Bleecker, A. B. (2006) · The Plant Cell · doi:10.1105/tpc.106.044537 · Cited by 190 · see citing works
Yang, H.-S., Jansen, A. P., Nair, R., Shibahara, K., Verma, A. K., Cmarik, J. L., & Colburn, N. H. (2001) · Oncogene · doi:10.1038/sj.onc.1204137 · Cited by 185 · see citing works
PDCD4 inhibits translation initiation by binding to eIF4A using both its MA3 domains
Suzuki, C., Garces, R. G., Edmonds, K. A., Hiller, S., Hyberts, S. G., Marintchev, A., & Wagner, G. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0712235105 · Cited by 165 · see citing works
Gallie, D., & Browning, K. S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m103869200 · Cited by 154 · see citing works
Self-citationWang, Q., Sun, Z., & Yang, H. (2007) · Oncogene · doi:10.1038/sj.onc.1210793 · Cited by 147 · see citing works
Wei, C., Balasta, M. L., Ren, J., & Goss, D. J. (1998) · Biochemistry · doi:10.1021/bi9724570 · Cited by 132 · see citing works
Structural basis for translational inhibition by the tumour suppressor Pdcd4
Loh, P. G., Yang, H., Walsh, M. A., Wang, Q., Wang, X., Cheng, Z., Liu, D. X., & Song, H. (2009) · The EMBO Journal · doi:10.1038/emboj.2008.278 · Cited by 125 · see citing works
LEI, G., SHEN, M., LI, Z., Zhang, B., Duan, K.-X., WANG, N., Cao, Y., Zhang, W., Ma, B., Ling, H., et al. (2011) · Plant Cell & Environment · doi:10.1111/j.1365-3040.2011.02363.x · Cited by 118 · see citing works
Timme, R. E. E., & Delwiche, C. (2010) · BMC Plant Biology · doi:10.1186/1471-2229-10-96 · Cited by 98 · see citing works
DUG is a novel homologue of translation initiation factor 4G that binds eIF4A
Göke, A., Göke, R., Knolle, A., Trusheim, H., Schmidt, H., Wilmen, A., Carmody, R. J., Göke, B., & Chen, Y. H. (2002) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)02129-0 · Cited by 92 · see citing works
Protein-protein interactions required during translation
Gallie, D. (2002) · Plant Molecular Biology · doi:10.1023/a:1021220910664 · Cited by 87 · see citing works
Self-citationKorneeva, N. L., First, E. A., Benoit, C. A., & Rhoads, R. E. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406168200 · Cited by 84 · see citing works
Lellis, A. D., Allen, M. L., Aertker, A. W., Tran, J., Hillis, D. M., Harbin, C. R., Caldwell, C., Gallie, D., & Browning, K. S. (2010) · Plant Molecular Biology · doi:10.1007/s11103-010-9670-z · Cited by 84 · see citing works
Self-citationCharacterization of the Two eIF4A-binding Sites on Human eIF4G-1
Korneeva, N. L., Lamphear, B. J., Hennigan, F. L. C., Merrick, W. C., & Rhoads, R. E. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m006345200 · Cited by 81 · see citing works
Structural Basis for Inhibition of Translation by the Tumor Suppressor Pdcd4
LaRonde-LeBlanc, N. A., Santhanam, A. N., Baker, A. R., Wlodawer, A., & Colburn, N. H. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00867-06 · Cited by 76 · see citing works
Bi, X., Ren, J., & Goss, D. J. (2000) · Biochemistry · doi:10.1021/bi992322p · Cited by 67 · see citing works
The Construction and Use of Log-Odds Substitution Scores for Multiple Sequence Alignment
Altschul, S. F., Wootton, J. C., Zaslavsky, E., & Yu, Y. (2010) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000852 · Cited by 64 · see citing works
Bellsolell, L., Cho-Park, P. F., Poulin, F., Sonenberg, N., & Burley, S. K. (2006) · Structure · doi:10.1016/j.str.2006.03.012 · Cited by 62 · see citing works
Waters, L. C., Veverka, V., Böhm, M., Schmedt, T., Choong, P. T., Muskett, F. W., Klempnauer, K.-H., & Carr, M. D. (2007) · Oncogene · doi:10.1038/sj.onc.1210305 · Cited by 48 · see citing works
Cheng, S., & Gallie, D. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m605404200 · Cited by 32 · see citing works
Self-citationCheng, S., & Gallie, D. (2010) · Biochemistry · doi:10.1021/bi1008529 · Cited by 27 · see citing works
Self-citationEukaryotic initiation factor 4B and the poly(A)-binding protein bind eIF4G competitively
Cheng, S., & Gallie, D. (2013) · Translation · doi:10.4161/trla.24038 · Cited by 20 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
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Matsuhashi, S., Manirujjaman, M., Hamajima, H., & Ozaki, I. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20092304 · Cited by 143 · see citing works
Phosphoproteomics Reveals the Effect of Ethylene in Soybean Root under Flooding Stress
Yin, X., Sakata, K., & Komatsu, S. (2014) · Journal of Proteome Research · doi:10.1021/pr500621c · Cited by 51 · see citing works
Lee, D., Park, S. J., Ahn, C. S., & Pai, H. (2017) · The Plant Cell · doi:10.1105/tpc.17.00563 · Cited by 47 · see citing works
Responses of Marine Diatom Skeletonema marinoi to Nutrient Deficiency: Programmed Cell Death
Wang, H., Chen, F., Mi, T., Liu, Q., Yu, Z., & Zhen, Y. (2019) · Applied and Environmental Microbiology · doi:10.1128/aem.02460-19 · Cited by 39 · see citing works
Yin, X., & Komatsu, S. (2017) · Journal of Proteomics · doi:10.1016/j.jprot.2017.01.014 · Cited by 36 · see citing works
The tip of the iceberg: emerging roles of TORC1, and its regulatory functions in plant cells
Pacheco, J. M., Canal, M. V., Pereyra, C. M., Welchen, E., Martínez-Noël, G. M. A., & Estevez, J. M. (2020) · Journal of Experimental Botany · doi:10.1093/jxb/eraa603 · Cited by 33 · see citing works
Zhao, Y., Tang, X., Lv, M., Liu, Q., Li, J., Zhang, B., Li, L., Zhang, X., & Zhao, Y. (2020) · Aquatic Toxicology · doi:10.1016/j.aquatox.2020.105669 · Cited by 31 · see citing works
Orefice, I., Lauritano, C., Procaccini, G., Ianora, A., & Romano, G. (2015) · Marine Genomics · doi:10.1016/j.margen.2015.06.008 · Cited by 25 · see citing works
Evolution and palaeophysiology of the vascular system and other means of long-distance transport
Raven, J. A. (2017) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2016.0497 · Cited by 24 · see citing works
Singh, P., Singh, A. P., Tripathi, S. K., Kumar, V., & Sane, A. P. (2019) · Plant Science · doi:10.1016/j.plantsci.2019.110242 · Cited by 15 · see citing works
Zhang, H., Liu, J., He, Y., Xie, Z.-X., Zhang, S., Zhang, Y., Lin, L., Liu, S., & Wang, D. (2019) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2019.04.216 · Cited by 15 · see citing works
Roles of plant hormones and anti-apoptosis genes during drought stress in rice (Oryza sativa L.)
Ubaidillah, M., Safitri, F. A., Jo, J.-H., Lee, S., Hussain, A., Mun, B., Chung, I. K., Yun, B., & Kim, K. (2016) · 3 Biotech · doi:10.1007/s13205-016-0564-x · Cited by 14 · see citing works
Dangwal, M., & Das, S. (2018) · Journal of Molecular Evolution · doi:10.1007/s00239-018-9863-7 · Cited by 13 · see citing works
Comparative Transcriptome Analysis to Reveal Genes Involved in Wheat Hybrid Necrosis
Zhang, Y., Cheng, Y., Guo, J., Yang, E., Liu, C., Zheng, X., Deng, K., & Zhou, J. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms151223332 · Cited by 9 · see citing works
Pernis, M., Škultéty, Ľ., Shevchenko, V., Klubicová, K., Rashydov, N. M., & Danchenko, M. (2020) · Journal of Plant Physiology · doi:10.1016/j.jplph.2020.153219 · Cited by 8 · see citing works
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Das, S. (2022) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-022-04464-7 · Cited by 5 · see citing works
Baraldi, E., Coller, E., Zoli, L., Cestaro, A., Tosatto, S. C. E., & Zambelli, B. (2015) · Plant Molecular Biology · doi:10.1007/s11103-015-0353-7 · Cited by 5 · see citing works
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Dangwal, M., Chahar, N., & Das, S. (2024) · Acta Physiologiae Plantarum · doi:10.1007/s11738-024-03734-9 · Cited by 1 · see citing works
Winterhagen, P., Hagemann, M. H., & Wünsche, J. N. (2019) · Acta Horticulturae · doi:10.17660/actahortic.2019.1242.66 · Cited by 1 · see citing works
Hegde, V., Sharma, D. K., Patel, H., Narasimha, P. L., Luddu, J., Mubaya, R., Holčı́k, M., & Thakor, N. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27093955
Kebede, F. G., Bantte, K., Mendaye, T. T., Menamo, T. M., & Bogale, M. (2025) · Industrial Crops and Products · doi:10.1016/j.indcrop.2025.122343
- Authors
- Cheng, S., Liu, R., & Gallie, D. R.
- Affiliations
- University of California, Riverside (US)
- Corresponding author
- Gallie, Daniel R
- Venue
- BMC Evolutionary Biology
- Published
- 2013-09-16
- Volume
- 13
- Issue
- 1
- Pages
- 199-199
- ISSN
- 1471-2148 (ISSN-L)
- PMC
- PMC3850090
- OpenAlex
- W2069441791
- Cited by
- 22
- References
- 43
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2022: 1 · 2020: 3 · 2019: 5 · 2018: 1 · 2017: 3 · 2016: 1 · 2015: 2 · 2014: 2
- FWCI
- 2.01
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- BMC Evolutionary Biology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Science Foundation (0820047)
- Division of Agriculture and Natural Resources, University of California
- Topics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Keywords
- PDCD4, eIF4G, eIF4A, translation initiation, gene duplication, land plant evolution, Chlorophyta, ethylene signaling, abiotic stress response, gene family evolution, protein evolution
- MeSH terms
- Amino Acid Sequence, Chlamydomonas, Molecular Sequence Data, Plant Proteins, Plants, RNA, Messenger, Protein Biosynthesis, Signal Transduction, Sequence Alignment, Apoptosis, Protein Structure, Tertiary, Evolution, Molecular, Eukaryotic Initiation Factor-4F, Apoptosis Regulatory Proteins
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