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Temperature sensitivity for conformation is an intrinsic property of wild-type p53.
The tumour-suppressor protein p53 is a metal-binding transcription factor with sequence-specific DNA-binding capacity. In cancer, mutation of p53 disrupts protein conformation with consequent loss of DNA binding and associated tumour-suppressor function. In vitro, the conformation and DNA-binding ac...
Autores principales: | , , |
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
1995
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2033583/ https://www.ncbi.nlm.nih.gov/pubmed/7841034 |
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author | Hainaut, P. Butcher, S. Milner, J. |
author_facet | Hainaut, P. Butcher, S. Milner, J. |
author_sort | Hainaut, P. |
collection | PubMed |
description | The tumour-suppressor protein p53 is a metal-binding transcription factor with sequence-specific DNA-binding capacity. In cancer, mutation of p53 disrupts protein conformation with consequent loss of DNA binding and associated tumour-suppressor function. In vitro, the conformation and DNA-binding activity of wild-type p53 are subject to redox modulation and are abrogated by exposure to metal chelators. In the present study, we have used the chelator 1, 10-phenanthroline (OP) to probe the effect of temperature on the conformational stability of p53 translated in vitro. Whereas low temperature (30 degrees C) stabilised wild-type p53 conformation and protected against chelation, high temperature (41 degrees C) promoted destabilisation and enhanced chelation, indicating that temperature influences the folding of wild-type p53. Destabilisation of p53 tertiary structure induced protein aggregation through hydrophobic interactions, consistent with the notion that wild-type p53 contains a hydrophobic core which may become exposed by metal chelation. These results indicate that temperature sensitivity for conformation is an intrinsic property of wild-type p53 and suggests that small changes in temperature may directly affect p53 function. IMAGES: |
format | Text |
id | pubmed-2033583 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1995 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-20335832009-09-10 Temperature sensitivity for conformation is an intrinsic property of wild-type p53. Hainaut, P. Butcher, S. Milner, J. Br J Cancer Research Article The tumour-suppressor protein p53 is a metal-binding transcription factor with sequence-specific DNA-binding capacity. In cancer, mutation of p53 disrupts protein conformation with consequent loss of DNA binding and associated tumour-suppressor function. In vitro, the conformation and DNA-binding activity of wild-type p53 are subject to redox modulation and are abrogated by exposure to metal chelators. In the present study, we have used the chelator 1, 10-phenanthroline (OP) to probe the effect of temperature on the conformational stability of p53 translated in vitro. Whereas low temperature (30 degrees C) stabilised wild-type p53 conformation and protected against chelation, high temperature (41 degrees C) promoted destabilisation and enhanced chelation, indicating that temperature influences the folding of wild-type p53. Destabilisation of p53 tertiary structure induced protein aggregation through hydrophobic interactions, consistent with the notion that wild-type p53 contains a hydrophobic core which may become exposed by metal chelation. These results indicate that temperature sensitivity for conformation is an intrinsic property of wild-type p53 and suggests that small changes in temperature may directly affect p53 function. IMAGES: Nature Publishing Group 1995-02 /pmc/articles/PMC2033583/ /pubmed/7841034 Text en https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Research Article Hainaut, P. Butcher, S. Milner, J. Temperature sensitivity for conformation is an intrinsic property of wild-type p53. |
title | Temperature sensitivity for conformation is an intrinsic property of wild-type p53. |
title_full | Temperature sensitivity for conformation is an intrinsic property of wild-type p53. |
title_fullStr | Temperature sensitivity for conformation is an intrinsic property of wild-type p53. |
title_full_unstemmed | Temperature sensitivity for conformation is an intrinsic property of wild-type p53. |
title_short | Temperature sensitivity for conformation is an intrinsic property of wild-type p53. |
title_sort | temperature sensitivity for conformation is an intrinsic property of wild-type p53. |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2033583/ https://www.ncbi.nlm.nih.gov/pubmed/7841034 |
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