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Tracing the Evolution of the p53 Tetramerization Domain
The tetrameric transcription factors p53, p63, and p73 evolved from a common ancestor and play key roles in tumor suppression and development. Surprisingly, p63 and p73 require a second helix in their tetramerization domain for the formation of stable tetramers that is absent in human p53, raising q...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4155161/ https://www.ncbi.nlm.nih.gov/pubmed/25185827 http://dx.doi.org/10.1016/j.str.2014.07.010 |
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author | Joerger, Andreas C. Wilcken, Rainer Andreeva, Antonina |
author_facet | Joerger, Andreas C. Wilcken, Rainer Andreeva, Antonina |
author_sort | Joerger, Andreas C. |
collection | PubMed |
description | The tetrameric transcription factors p53, p63, and p73 evolved from a common ancestor and play key roles in tumor suppression and development. Surprisingly, p63 and p73 require a second helix in their tetramerization domain for the formation of stable tetramers that is absent in human p53, raising questions about the evolutionary processes leading to diversification. Here we determined the crystal structure of the zebrafish p53 tetramerization domain, which contains a second helix, reminiscent of p63 and p73, combined with p53-like features. Through comprehensive phylogenetic analyses, we systematically traced the evolution of vertebrate p53 family oligomerization domains back to the beginning of multicellular life. We provide evidence that their last common ancestor also had an extended p63/p73-like domain and pinpoint evolutionary events that shaped this domain during vertebrate radiation. Domain compaction and transformation of a structured into a flexible, intrinsically disordered region may have contributed to the expansion of the human p53 interactome. |
format | Online Article Text |
id | pubmed-4155161 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-41551612014-09-06 Tracing the Evolution of the p53 Tetramerization Domain Joerger, Andreas C. Wilcken, Rainer Andreeva, Antonina Structure Article The tetrameric transcription factors p53, p63, and p73 evolved from a common ancestor and play key roles in tumor suppression and development. Surprisingly, p63 and p73 require a second helix in their tetramerization domain for the formation of stable tetramers that is absent in human p53, raising questions about the evolutionary processes leading to diversification. Here we determined the crystal structure of the zebrafish p53 tetramerization domain, which contains a second helix, reminiscent of p63 and p73, combined with p53-like features. Through comprehensive phylogenetic analyses, we systematically traced the evolution of vertebrate p53 family oligomerization domains back to the beginning of multicellular life. We provide evidence that their last common ancestor also had an extended p63/p73-like domain and pinpoint evolutionary events that shaped this domain during vertebrate radiation. Domain compaction and transformation of a structured into a flexible, intrinsically disordered region may have contributed to the expansion of the human p53 interactome. Cell Press 2014-09-02 /pmc/articles/PMC4155161/ /pubmed/25185827 http://dx.doi.org/10.1016/j.str.2014.07.010 Text en © 2014 The Authors https://creativecommons.org/licenses/by/3.0/This work is licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/) . |
spellingShingle | Article Joerger, Andreas C. Wilcken, Rainer Andreeva, Antonina Tracing the Evolution of the p53 Tetramerization Domain |
title | Tracing the Evolution of the p53 Tetramerization Domain |
title_full | Tracing the Evolution of the p53 Tetramerization Domain |
title_fullStr | Tracing the Evolution of the p53 Tetramerization Domain |
title_full_unstemmed | Tracing the Evolution of the p53 Tetramerization Domain |
title_short | Tracing the Evolution of the p53 Tetramerization Domain |
title_sort | tracing the evolution of the p53 tetramerization domain |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4155161/ https://www.ncbi.nlm.nih.gov/pubmed/25185827 http://dx.doi.org/10.1016/j.str.2014.07.010 |
work_keys_str_mv | AT joergerandreasc tracingtheevolutionofthep53tetramerizationdomain AT wilckenrainer tracingtheevolutionofthep53tetramerizationdomain AT andreevaantonina tracingtheevolutionofthep53tetramerizationdomain |