ArticleProtein science : a publication of the Protein Society2006
Folding and misfolding mechanisms of the p53 DNA binding domain at physiological temperature.
Article in Protein science : a publication of the Protein Society, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Restoration of the Y220C p53 Full-Length Mutant by PK11000: a Molecular Dynamics Study of an Intrinsically Disordered Protein.ACS omega · 2026Article
- Navigating the complexity of p53-DNA binding: implications for cancer therapy.Biophysical reviews · 2024Review
- Cell fate regulation governed by p53: Friends or reversible foes in cancer therapy.Cancer communications (London, England) · 2024Review
- Amyloid aggregates induced by the p53-R280T mutation lead to loss of p53 function in nasopharyngeal carcinoma.Cell death & disease · 2024Article
- A role for bioinorganic chemistry in the reactivation of mutant p53 in cancer.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2022Review
- Interdiction in the Early Folding of the p53 DNA-Binding Domain Leads to Its Amyloid-Like Misfolding.Molecules (Basel, Switzerland) · 2022Article
- Most Probable Druggable Pockets in Mutant p53-Arg175His Clusters Extracted from Gaussian Accelerated Molecular Dynamics Simulations.The protein journal · 2022Article
- Article
- Review
- Aggregation of zinc-free p53 is inhibited by Hsp90 but not other chaperones.Protein science : a publication of the Protein Society · 2019Article
- Cryo-LESA Mass Spectrometry-a Step Towards Truly Native Surface Sampling of Proteins.Journal of the American Society for Mass Spectrometry · 2019Article
- p53 amyloid formation leading to its loss of function: implications in cancer pathogenesis.Cell death and differentiation · 2017Article
- Folding of a cyclin box: linking multitarget binding to marginal stability, oligomerization, and aggregation of the retinoblastoma tumor suppressor AB pocket domain.The Journal of biological chemistry · 2013Article
- Interaction of the p53 DNA-binding domain with its n-terminal extension modulates the stability of the p53 tetramer.Journal of molecular biology · 2011Article
- Article
- Effects of temperature on the p53-DNA binding interactions and their dynamical behavior: comparing the wild type to the R248Q mutant.PloS one · 2011Article
- Cancer biomarker discovery: the entropic hallmark.PloS one · 2010Article
- Hsp70 molecular chaperones are required to support p53 tumor suppressor activity under stress conditions.Oncogene · 2009Article
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2 authors.
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Abstract
p53 modulates a large number of cellular response pathways and is critical for the prevention of cancer. Wild-type p53, as well as tumorigenic mutants, exhibits the singular property of spontaneously losing DNA binding activity at 37 degrees C. To understand the molecular basis for this effect, we examine the folding mechanism of the p53 DNA binding domain (DBD) at elevated temperatures. Folding kinetics do not change appreciably from 5 degrees C to 35 degrees C. DBD therefore folds by the same two-channel mechanism at physiological temperature as it does at 10 degrees C. Unfolding rates, however, accelerate by 10,000-fold. Elevated temperatures thus dramatically increase the frequency of cycling between folded and unfolded states. The results suggest that function is lost because a fraction of molecules become trapped in misfolded conformations with each folding-unfolding cycle. In addition, at 37 degrees C, the equilibrium stabilities of the off-pathway species are predicted to rival that of the native state, particularly in the case of destabilized mutants. We propose that it is the presence of these misfolded species, which can aggregate in vitro and may be degraded in the cell, that leads to p53 inactivation.
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