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Cancer-derived p53 mutants suppress p53-target gene expression--potential mechanism for gain of function of mutant p53
Open accessAbstract
Tumour-derived p53 mutants are thought to have acquired 'gain-of-function' properties that contribute to oncogenicity. We have tested the hypothesis that p53 mutants suppress p53-target gene expression, leading to enhanced cellular growth. Silencing of mutant p53 expression in several human cell lines was found to lead to the upregulation of wild-type p53-target genes such as p21, gadd45, PERP and PTEN. The expression of these genes was also suppressed in H1299-based isogenic cell lines expressing various hot-spot p53 mutants, and silencing of mutant p53, but not TAp73, abrogated the suppression. Consistently, these hot-spot p53 mutants were able to suppress a variety of p53-target gene promoters. Analysis using the proto-type p21 promoter construct indicated that the p53-binding sites are dispensable for mutant p53-mediated suppression. However, treatment with the histone deacetylase inhibitor trichostatin-A resulted in relief of mutant p53-mediated suppression, suggesting that mutant p53 may induce hypo-acetylation of target gene promoters leading to the suppressive effects. Finally, we show that stable down-regulation of mutant p53 expression resulted in reduced cellular colony growth in human cancer cells, which was found to be due to the induction of apoptosis. Together, the results demonstrate another mechanism through which p53 mutants could promote cellular growth.
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“Furthermore, GOF mut-p53 has been shown to abnormally regulate a multitude of genes that play critical roles in GBM pathogenesis, but have not been analyzed in the context of GBM. This includes CD95/Fas/Apo1, PARP, PTEN, and more [63,94,95,96,97,98].”
From The p53 Pathway in Glioblastoma (2018) · cites this paper as [98]
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Vogelstein, B., Lane, D., & Levine, A. J. (2000) · Nature · doi:10.1038/35042675 · Cited by 6,607 · cited 2×
“Mutations in p53 have been shown to abrogate its cardinal functions in promoting apoptosis, cell-cycle arrest and DNA repair, thereby leading to cancer development and progression (1, 2 ).”
BackgroundMdm2 promotes the rapid degradation of p53
Haupt, Y., Maya, R., Kazaz, A., & Oren, M. (1997) · Nature · doi:10.1038/387296a0 · Cited by 4,506
A System for Stable Expression of Short Interfering RNAs in Mammalian Cells
Brummelkamp, T. R., Bernards, R., & Agami, R. (2002) · Science · doi:10.1126/science.1068999 · Cited by 4,295
Regulation of p53 stability by Mdm2
Kubbutat, M. H. G., Jones, S. N., & Vousden, K. H. (1997) · Nature · doi:10.1038/387299a0 · Cited by 3,312 · cited 2×
“Mutated p53 is often overexpressed in tumour cells (1,2,6), due to their inability to effectively activate MDM2, which negatively regulates p53 abundance (7,8).”
BackgroundLive or let die: the cell's response to p53
Vousden, K. H., & Lü, X. (2002) · Nature reviews. Cancer · doi:10.1038/nrc864 · Cited by 3,231
p300/CBP proteins: HATs for transcriptional bridges and scaffolds
Chan, H. M., & La Thangue, N. B. (2001) · Journal of Cell Science · doi:10.1242/jcs.114.13.2363 · Cited by 1,092
Restoration of the tumor suppressor function to mutant p53 by a low-molecular-weight compound
Bykov, V. J. N., Issaeva, N., Shilov, A., Hultcrantz, M., Pugacheva, E., Chumakov, P., Bergman, J., Wiman, K. G., & Selivanova, G. (2002) · Nature Medicine · doi:10.1038/nm0302-282 · Cited by 1,067
Role for the p53 homologue p73 in E2F-1-induced apoptosis
Irwin, M. S., Marín, M. C., Phillips, A. C., Seelan, R. S., Smith, D. I., Liu, W., Flores, E. R., Tsai, K. Y., Jacks, T., Vousden, K. H., et al. (2000) · Nature · doi:10.1038/35036614 · Cited by 710
Oncogenic mutations of the p53 tumor suppressor: the demons of the guardian of the genome.
Sigal, A., & Rotter, V. (2000) · PubMed · Cited by 669
Mutations truncating the EP300 acetylase in human cancers
Gayther, S. A., Batley, S. J., Linger, L., Bannister, A. J., Thorpe, K. L., Chin, S., Daigo, Y., Russell, P. A., Wilson, A., Sowter, H., et al. (2000) · Nature Genetics · doi:10.1038/73536 · Cited by 588
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Items 101–146 of 146
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Dartora, V. F. C., Passos, J. S., Costa-Lotufo, L. V., Lopes, L. B., & Panitch, A. (2024) · Pharmaceutics · doi:10.3390/pharmaceutics16020231 · Cited by 14
Mutant p53: evolving perspectivesPreprint
Efe, G., Cunningham, K. M., Rustgi, A. K., Prives, C. L., Manfredi, J. J., & Rivera, F. J. S. (2025) · Genes & Development · doi:10.1101/gad.353408.125 · Cited by 16
Chen, Z., Ge, Q., Wang, C., Ruan, Y., Liu, J., & Ye, Z. (2016) · OncoTargets and Therapy · doi:10.2147/ott.s96710 · Cited by 11
Rostami, A., Palomer, X., Pizarro‐Delgado, J., Peña, L., Zamora, M., Montori-Grau, M., Barroso, E., Valenzuela‐Alcaráz, B., Crispi, F., Salvador, J. M., et al. (2025) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-025-05704-x · Cited by 11
Wei, L., Lao, Y., Fu, T., Xie, Z., Wang, Y., Yang, T., Huang, L., Liu, J., Shu, M., Tian, T., et al. (2025) · Clinical Lung Cancer · doi:10.1016/j.cllc.2025.04.007 · Cited by 9
p53: Balancing tumour suppression and implications for the clinic
Buganim, Y., & Rotter, V. (2009) · European Journal of Cancer · doi:10.1016/s0959-8049(09)70037-1 · Cited by 9
Mechanism of RCD and the Role of Different Death Signaling Pathways in Cancer
Zhou, J., Huang, R., Aimaiti, M., Zhou, Q., Wu, X. Y., Zhu, J., Ma, X., Qian, K., Zhou, Q., Hu, L., et al. (2025) · Biomedicines · doi:10.3390/biomedicines13081880 · Cited by 8
Qian, H., Hou, C., Zhang, Y., Ji, S., Zhong, C., Li, J., Zhang, Q., Huang, J., Li, C., & ChengJi (2023) · Cancer Genetics · doi:10.1016/j.cancergen.2023.08.006 · Cited by 8
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Otto, N., Schulz, P. M., Scholz, A., Hauff, P., Schlegelberger, B., Detjen, K. M., & Wiedenmann, B. J. (2011) · British Journal of Cancer · doi:10.1038/bjc.2011.521 · Cited by 7
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Bostan, M., Mihaila, M. A., Hotnog, C. M., Bleoţu, C., Anton, G., Roman, V., & Braşoveanu, L. I. (2016) · InTech eBooks · doi:10.5772/63382 · Cited by 6
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Adebayo, I. A., Arsad, H., & Samian, M. R. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-824109-7.00008-x · Cited by 4
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Self-citationWu, G., Zhang, M., Meng, Y., Ying, Y., Zhang, S., Chen, M., Li, D., Yang, S., & Luo, M. (2023) · Research Square · doi:10.21203/rs.3.rs-3174433/v1 · Cited by 2
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Jaber, S., Eldawra, E., Rakotopare, J., Simeonova, I., Lejour, V., Gabriel, M., Cañeque, T., Volochtchouk, V., Licaj, M., Fajac, A., et al. (2025) · eLife · doi:10.7554/elife.102434.3 · Cited by 1
Wang, Z., Vaillant, F., Chang, C. W. T., Riffkin, C. D., Lieschke, E., Diepstraten, S. T., Huang, D. C. S., Visvader, J. E., Herold, M. J., Kelly, G. L., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.03.30.015263 · Cited by 1
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Husaini, R. (2014) · Bradford Scholars (University of Bradford)
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Wagh, A. R., & Bose, K. (2019) · Springer eBooks · doi:10.1007/978-981-32-9816-3_5
Yasin, D., Zafaryab, M., Fakhri, K. U., Husain, S., Afzal, B., Sami, N., Hemlata, H., Rizvi, M. M. A., & Fatma, T. (2020) · Advances in medical diagnosis, treatment, and care (AMDTC) book series · doi:10.4018/978-1-7998-6530-8.ch009
di Fagagna, F. D., & Ogrunc, M. (2013) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.718031533.793488399
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李, 苗. (2022) · Advances in Clinical Medicine · doi:10.12677/acm.2022.125547
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Jaber, S., Eldawra, E., Rakotopare, J., Gabriel, M., Lejour, V., Simeonova, I., Morillon, A., Bardot, B., & Toledo, F. (2024) · eLife · doi:10.7554/elife.102434.1
Jaber, S., Eldawra, E., Rakotopare, J., Simeonova, I., Lejour, V., Gabriel, M., Cañeque, T., Volochtchouk, V., Licaj, M., Fajac, A., et al. (2025) · eLife · doi:10.7554/elife.102434.2
Helmy, W. A., Diab, M. S. M., Sherif, N. H., Mohamed, M. A. E. H., Hawas, A. M., Hasaballah, A. A., & El-Hameid, A. R. A. (2025) · South African Journal of Botany · doi:10.1016/j.sajb.2025.03.054
Rakotopare, J. (2024) · theses.fr (ABES) · doi:10.70675/cc79cc10zbaf8z4e88za003z8a8d37707576
Acosta-Dent, A., Garcı́a-Villa, E., Cotino‐Nájera, S., Lizcano‐Meneses, S., Lagunas‐Rangel, F. A., Garrido‐Guerrero, E., Díaz‐Chávez, J., & Gariglio, P. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27104481
Quantitative proteomic landscape reveals the role of CSPG5 in the recurrence of glioma
Wang, S., Tian, B., Liu, H., Zhang, C., Wang, J., Song, X., Li, R., Guo, H., Wang, N., Zhang, W., et al. (2026) · Cancer Cell International · doi:10.1186/s12935-026-04430-z
Characterisation of a novel p53 mutation (p53N263Tfs*7) associated with li-fraumeni syndrome
Wright, F. M., Vasileva‐Slaveva, M., Yordanov, A. D., Ivanov, I. F., Gorcheva, Z., Mohr, A., Wright, G. S. A., Brooke, G. N., & Metodiev, M. V. (2026) · BMC Cancer · doi:10.1186/s12885-026-16582-2
BindingDB (2018) · UC San Diego · doi:10.7270/q2vh5qtw
Metadata
- Authors
- Vikhanskaya, F., Lee, M. K., Mazzoletti, M., Broggini, M., & Sabapathy, K.
- Affiliations
- National Cancer Centre Singapore (SG)
- National University of Singapore (SG)
- Corresponding author
- Sabapathy, K.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-03-01
- Volume
- 35
- Issue
- 6
- Pages
- 2093-2104
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC1874625
- OpenAlex
- W2111523470
- Cited by
- 145
- References
- 38
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 8 · 2023: 6 · 2022: 6 · 2021: 4 · 2020: 8 · 2019: 6 · 2018: 9 · 2017: 9 · 2016: 12 · 2015: 10 · 2014: 12 · 2013: 11 · 2012: 4
- FWCI
- 3.21
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- Nucleic Acids Research (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- National University of Singapore (submittedVersion)
- Funders
- Medical Research Council
- National Medical Research Council
- 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 › Heat shock proteins research
- Keywords
- mutant p53, gain-of-function, p21, GADD45, PERP, PTEN, p53 binding sites, histone deacetylation, trichostatin A, apoptosis, cell growth, TAp73
- MeSH terms
- Binding Sites, Enzyme Inhibitors, Humans, Hydroxamic Acids, Mutation, Neoplasms, Promoter Regions, Genetic, Down-Regulation, Gene Expression Regulation, Neoplastic, Genes, p53, Tumor Suppressor Protein p53, Apoptosis, RNA Interference, Cell Line, Tumor, Cyclin-Dependent Kinase Inhibitor p21, Histone Deacetylase Inhibitors
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