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The first 30 years of p53: growing ever more complex.
Open accessAbstract
Thirty years ago p53 was discovered as a cellular partner of simian virus 40 large T-antigen, the oncoprotein of this tumour virus. The first decade of p53 research saw the cloning of p53 DNA and the realization that p53 is not an oncogene but a tumour suppressor that is very frequently mutated in human cancer. In the second decade of research, the function of p53 was uncovered: it is a transcription factor induced by stress, which can promote cell cycle arrest, apoptosis and senescence. In the third decade after its discovery new functions of this protein were revealed, including the regulation of metabolic pathways and cytokines that are required for embryo implantation. The fourth decade of research may see new p53-based drugs to treat cancer. What is next is anybody's guess.
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“Both these pathways are complex as they involve many upstream regulators and downstream effectors along with varying side branches (Chau and Wang, 2003; Levine and Oren, 2009).”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as Levine and Oren, 2009
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Pan, M., Jiang, C., Zhang, Z., Achacoso, N. S., Alexeeff, S., Solorzano, A. V., Tse, P., Chung, E. H., Sundaresan, T. K., Suga, J. M., et al. (2023) · JCO Precision Oncology · doi:10.1200/po.22.00570 · Cited by 38
Hao, X., Bahia, R. K., Cseh, O., Bozek, D. A., Blake, S., Rinnenthal, J., Weyer-Czernilofsky, U., Rudolph, D., & Artee Luchman, H. (2023) · Neuro-Oncology · doi:10.1093/neuonc/noac271 · Cited by 34
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Levav-Cohen, Y., Goldberg, Z., Tan, K. H., Alsheich-Bartok, O., Zuckerman, V., Haupt, S., & Haupt, Y. (2014) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-94-017-9211-0_9 · Cited by 38
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Shi, H., Gao, Y., Tang, Y., Wu, Y., Gong, H., Du, J. T., Zheng, B., Hu, J., Shi, Q., & Yu, R. (2014) · IUBMB Life · doi:10.1002/iub.1263 · Cited by 35
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Pan, Z., & Chang, C. C. (2011) · Autoimmunity Reviews · doi:10.1016/j.autrev.2011.12.004 · Cited by 36
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Hao, Q., & Cho, W. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms151222109 · Cited by 38
Schilling, T., Kairat, A., Melino, G., Krammer, P. H., Stremmel, W., Oren, M., & Müller, M. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.03.082 · Cited by 36
Self-citationGenetic background influences susceptibility to chemotherapy-induced hematotoxicity
Gatti, D. M., Weber, S. N., Goodwin, N. C., Lammert, F., & Churchill, G. A. (2017) · The Pharmacogenomics Journal · doi:10.1038/tpj.2017.23 · Cited by 33
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Wang, W., Zhang, A., Hao, Y., Wang, G., & Jia, Z. (2018) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.13788 · Cited by 35
KDM5A Regulates a Translational Program that Controls p53 Protein Expression
Hu, D., Jablonowski, C. M., Cheng, P.-H., AlTahan, A. M., Li, C., Wang, Y., Palmer, L. E., Lan, C., Sun, B., Abu‐Zaid, A., et al. (2018) · iScience · doi:10.1016/j.isci.2018.10.012 · Cited by 34
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Han, A., Li, C., Zahed, T., Wong, M. K., Smith, I. F., Hoedel, K., Green, D. R., & Boiko, A. D. (2019) · PLoS Biology · doi:10.1371/journal.pbio.3000402 · Cited by 36
p63 Is a Promising Marker in the Diagnosis of Unusual Skin Cancer
Smirnov, A., Anemona, L., Novelli, F., Piro, M. C., Annicchiarico‐Petruzzelli, M., Melino, G., & Candi, E. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20225781 · Cited by 35
Metadata
- Authors
- Levine, A. J., & Oren, M.
- Affiliations
- Institute for Advanced Study (US)
- Weizmann Institute of Science (IL)
- Venue
- Nature Reviews Cancer
- Published
- 2009-10
- Volume
- 9
- Issue
- 10
- Pages
- 749-758
- ISSN
- 1474-175X (ISSN-L)
- 1474-1768
- PMC
- PMC2771725
- OpenAlex
- W1966163762
- Cited by
- 1,967
- References
- 169
- Citations by year
- 2026: 64 · 2025: 111 · 2024: 107 · 2023: 112 · 2022: 114 · 2021: 129 · 2020: 128 · 2019: 111 · 2018: 127 · 2017: 120 · 2016: 144 · 2015: 115 · 2014: 150 · 2013: 113 · 2012: 170
- FWCI
- 9.34
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Cancer (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (P01CA087497, R37 CA40099, R37CA040099, P01CA87497.)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- p53, TP53, tumour suppressor, SV40 large T antigen, transcription factors, cell cycle arrest, apoptosis, cellular senescence, metabolic regulation, cytokine regulation, embryo implantation
- MeSH terms
- Animals, Humans, Neoplasms, Genes, p53, Tumor Suppressor Protein p53, History, 20th Century, History, 21st Century
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