Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Joerger, Andreas C., Wilcken, Rainer, Andreeva, Antonina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2014
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
_version_ 1782333548359843840
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