The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Thermodynamic stability of wild-type and mutant p53 core domain
Open accessAbstract
Some 50% of human cancers are associated with mutations in the core domain of the tumor suppressor p53. Many mutations are thought just to destabilize the protein. To assess this and the possibility of rescue, we have set up a system to analyze the stability of the core domain and its mutants. The use of differential scanning calorimetry or spectroscopy to measure its melting temperature leads to irreversible denaturation and aggregation and so is useful as only a qualitative guide to stability. There are excellent two-state denaturation curves on the addition of urea that may be analyzed quantitatively. One Zn 2+ ion remains tightly bound in the holo-form of p53 throughout the denaturation curve. The stability of wild type is 6.0 kcal (1 kcal = 4.18 kJ)/mol at 25°C and 9.8 kcal/mol at 10°C. The oncogenic mutants R175H, C242S, R248Q, R249S, and R273H are destabilized by 3.0, 2.9, 1.9, 1.9, and 0.4 kcal/mol, respectively. Under certain denaturing conditions, the wild-type domain forms an aggregate that is relatively highly fluorescent at 340 nm on excitation at 280 nm. The destabilized mutants give this fluorescence under milder denaturation conditions.
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“R248Q and R249S have similar thermodynamic stability and are both ≈2 kcal/mol less stable than the wild type (7).”
From Hot-spot mutants of p53 core domain evince characteristic local structural changes (1999) · cites this paper as [7]
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Cites
Lane, D. P. (1992) · Nature · doi:10.1038/358015a0 · Cited by 5,138
Self-citationMdm2 promotes the rapid degradation of p53
Haupt, Y., Maya, R., Kazaz, A., & Oren, M. (1997) · Nature · doi:10.1038/387296a0 · Cited by 4,506
Crystal Structure of a p53 Tumor Suppressor-DNA Complex: Understanding Tumorigenic Mutations
Cho, Y., Gorina, S., Jeffrey, P. D., & Pavletich, N. P. (1994) · Science · doi:10.1126/science.8023157 · Cited by 2,551
Cited by
Muller, P. A. J., & Vousden, K. H. (2013) · Nature Cell Biology · doi:10.1038/ncb2641 · Cited by 1,647
Targeting p53 pathways: mechanisms, structures, and advances in therapy
Wang, H., Guo, M., Wei, H., & Chen, Y. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01347-1 · Cited by 1,016
Gain of function of mutant p53 by coaggregation with multiple tumor suppressors
Xu, J., Reumers, J., Couceiro, J. R., De Smet, F., Gallardo, R., Rudyak, S., Cornelis, A., Rozenski, J., Zwolinska, A., Marine, J.-C., et al. (2011) · Nature Chemical Biology · doi:10.1038/nchembio.546 · Cited by 543
Gaiddon, C., Lokshin, M., Ahn, J., Zhang, T., & Prives, C. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.5.1874-1887.2001 · Cited by 464
A Designed Inhibitor of p53 Aggregation Rescues p53 Tumor Suppression in Ovarian Carcinomas
Soragni, A., Janzen, D. M., Johnson, L. M., Lindgren, A. G., Thai-Quynh Nguyen, A., Tiourin, E., Soriaga, A. B., Lu, J., Jiang, L., Faull, K. F., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2015.12.002 · Cited by 341
Soussi, T., & Wiman, K. G. (2015) · Cell Death & Differentiation · doi:10.1038/cdd.2015.53 · Cited by 305
APR-246 reactivates mutant p53 by targeting cysteines 124 and 277
Zhang, Q., Bykov, V. J. N., Wiman, K. G., & Zawacka-Pankau, J. (2018) · Cell Death & Disease · doi:10.1038/s41419-018-0463-7 · Cited by 261
Hot-spot mutants of p53 core domain evince characteristic local structural changes
Wong, K.-B., DeDecker, B. S., Freund, S. M. V., Proctor, M. R., Bycroft, M., & Fersht, A. R. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.15.8438 · Cited by 221
Self-citationReactivation of mutant p53: molecular mechanisms and therapeutic potential
Selivanova, G., & Wiman, K. G. (2007) · Oncogene · doi:10.1038/sj.onc.1210295 · Cited by 186
Solution structure of p53 core domain: Structural basis for its instability
Cañadillas, J. M. P., Tidow, H., Freund, S. M. V., Rutherford, T. J., Ang, H. C., & Fersht, A. R. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510941103 · Cited by 174
Self-citationDegtjarik, O., Golovenko, D., Diskin-Posner, Y., Abrahmsén, L., Rozenberg, H., & Shakked, Z. (2021) · Nature Communications · doi:10.1038/s41467-021-27142-6 · Cited by 78
(2019) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2019.08.002 · Cited by 78
Secondary interaction between MDMX and p53 core domain inhibits p53 DNA binding.
Wei, X., Wu, S., Song, T., Chen, L., Gao, M., Borcherds, W., Daughdrill, G. W., & Chen, J. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1603838113 · Cited by 50
Metadata
- Authors
- Bullock, A. N., Henckel, J., DeDecker, B. S., Johnson, C. M., Nikolova, P. V., Proctor, M. R., Lane, D. P., & Fersht, A. R.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1997-12-23
- Volume
- 94
- Issue
- 26
- Pages
- 14338-14342
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2081288740
- Cited by
- 405
- References
- 3
- FWCI
- 3.29
- Type
- journal article
- Language
- en
- Open access
- green
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