The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
Trim24 targets endogenous p53 for degradation
Open accessAbstract
Numerous studies focus on the tumor suppressor p53 as a protector of genomic stability, mediator of cell cycle arrest and apoptosis, and target of mutation in 50% of all human cancers. The vast majority of information on p53, its protein-interaction partners and regulation, comes from studies of tumor-derived, cultured cells where p53 and its regulatory controls may be mutated or dysfunctional. To address regulation of endogenous p53 in normal cells, we created a mouse and stem cell model by knock-in (KI) of a tandem-affinity-purification (TAP) epitope at the endogenous Trp-53 locus. Mass spectrometry of TAP-purified p53-complexes from embryonic stem cells revealed Tripartite-motif protein 24 (Trim24), a previously unknown partner of p53. Mutation of TRIM24 homolog, bonus , in Drosophila led to apoptosis, which could be rescued by p53-depletion. These in vivo analyses establish TRIM24/bonus as a pathway that negatively regulates p53 in Drosophila . The Trim24-p53 link is evolutionarily conserved, as TRIM24 depletion in human breast cancer cells caused p53-dependent, spontaneous apoptosis. We found that Trim24 ubiquitylates and negatively regulates p53 levels, suggesting Trim24 as a therapeutic target to restore tumor suppression by p53.
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“TRIM24 can bind an acetylated peptide of the tumour suppressor p53, leading to ubiquitylation and degradation of the target 130 .”
From Targeted protein degradation: expanding the toolbox (2019) · cites this paper as [130]
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The p53 tumour suppressor gene
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The Tandem Affinity Purification (TAP) Method: A General Procedure of Protein Complex Purification
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“Mdm2 is clearly chief among the previously identified negative regulators of p53 levels, for example, PirH2, ARF-BP1, Cop1, and others (17, 18, 35).”
BackgroundThe tripartite motif family identifies cell compartments
Reymond, A., Meroni, G., Fantozzi, A., Merla, G., Cairo, S., Luzi, L., Riganelli, D., Zanaria, E., Messali, S., Cainarca, S., et al. (2001) · The EMBO Journal · doi:10.1093/emboj/20.9.2140 · Cited by 1,366
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Rescue of embryonic lethality in Mdm2-deficient mice by absence of p53
Jones, S. N., Roe, A. E., Donehower, L. A., & Bradley, A. (1995) · Nature · doi:10.1038/378206a0 · Cited by 1,280 · cited 2×
“Mdm2 is clearly chief among the previously identified negative regulators of p53 levels, for example, PirH2, ARF-BP1, Cop1, and others (17, 18, 35).”
BackgroundGain of function of a p53 hot spot mutation in a mouse model of Li-Fraumeni syndrome
Lang, G. A., Iwakuma, T., Suh, Y.-A., Liu, G., Rao, V. A., Parant, J. M., Valentin-Vega, Y. A., Terzian, T., Caldwell, L. C., Strong, L. C., et al. (2004) · Cell · doi:10.1016/j.cell.2004.11.006 · Cited by 1,069
Mosaic analysis with a repressible cell marker (MARCM) for Drosophila neural development
Lee, T., & Luo, L. (2001) · Trends in Neurosciences · doi:10.1016/s0166-2236(00)01791-4 · Cited by 928
p53 ubiquitination: Mdm2 and beyond
Brooks, C. L., & Gu, W. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.01.020 · Cited by 924
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TRIM Family Proteins: Roles in Autophagy, Immunity, and Carcinogenesis
Hatakeyama, S. (2017) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2017.01.002 · Cited by 955
Targeted protein degradation: expanding the toolbox
Schapira, M., Calabrese, M. F., Bullock, A. N., & Crews, C. M. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0047-y · Cited by 960
Hatakeyama, S. (2011) · Nature reviews. Cancer · doi:10.1038/nrc3139 · Cited by 805
The p53 Pathway: Origins, Inactivation in Cancer, and Emerging Therapeutic Approaches
Joerger, A. C., & Fersht, A. R. (2016) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060815-014710 · Cited by 675
The role of ubiquitination and deubiquitination in cancer metabolism
Sun, T., Liu, Z., & Yang, Q. (2020) · Molecular Cancer · doi:10.1186/s12943-020-01262-x · Cited by 523
Metadata
- Authors
- Allton, K., Jain, A. K., Herz, H.-M., Tsai, W.-W., Jung, S. Y., Qin, J., Bergmann, A., Johnson, R. L., & Barton, M. C.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- The University of Texas Health Science Center at Houston (US)
- Baylor College of Medicine (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-07-14
- Volume
- 106
- Issue
- 28
- Pages
- 11612-11616
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2710642
- OpenAlex
- W2037942882
- Cited by
- 292
- References
- 40
- Citations by year
- 2026: 7 · 2025: 24 · 2024: 8 · 2023: 25 · 2022: 15 · 2021: 20 · 2020: 23 · 2019: 12 · 2018: 17 · 2017: 23 · 2016: 15 · 2015: 13 · 2014: 16 · 2013: 11 · 2012: 28
- FWCI
- 10.48
- 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
- National Institute of General Medical Sciences (GM081627, P01GM081627, GM068016, R01GM068016)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- TRIM24, p53, protein degradation, ubiquitination, tumor suppressor regulation, Drosophila, embryonic stem cells, tandem affinity purification, tumor suppression, breast cancer, apoptosis
- MeSH terms
- Animals, Chromatography, Gel, Drosophila, Humans, Mutation, Mass Spectrometry, Immunoblotting, Tumor Suppressor Protein p53, Apoptosis, Drosophila Proteins, Ubiquitin-Protein Ligases, Cell Line, Tumor, Chromatin Immunoprecipitation, Mice, Ubiquitination, Gene Knock-In Techniques
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