TCTP contains a BH3-like domain, which instead of inhibiting, activates Bcl-xL
Translationally Controlled Tumor Protein (TCTP) is anti-apoptotic, key in development and cancer, however without the typical Bcl2 family members’ structure. Here we report that TCTP contains a BH3-like domain and forms heterocomplexes with Bcl-xL. The crystal structure of a Bcl-xL deletion variant-...
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| Format: | Online |
| Language: | English |
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Nature Publishing Group
2016
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728560/ |
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pubmed-4728560 |
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pubmed-47285602016-02-01 TCTP contains a BH3-like domain, which instead of inhibiting, activates Bcl-xL Thébault, Stéphanie Agez, Morgane Chi, Xiaoke Stojko, Johann Cura, Vincent Telerman, Stéphanie B. Maillet, Laurent Gautier, Fabien Billas-Massobrio, Isabelle Birck, Catherine Troffer-Charlier, Nathalie Karafin, Teele Honoré, Joane Senff-Ribeiro, Andrea Montessuit, Sylvie Johnson, Christopher M. Juin, Philippe Cianférani, Sarah Martinou, Jean-Claude Andrews, David W. Amson, Robert Telerman, Adam Cavarelli, Jean Article Translationally Controlled Tumor Protein (TCTP) is anti-apoptotic, key in development and cancer, however without the typical Bcl2 family members’ structure. Here we report that TCTP contains a BH3-like domain and forms heterocomplexes with Bcl-xL. The crystal structure of a Bcl-xL deletion variant-TCTP11–31 complex reveals that TCTP refolds in a helical conformation upon binding the BH3-groove of Bcl-xL, although lacking the h1-subregion interaction. Experiments using in vitro-vivo reconstituted systems and TCTP+/− mice indicate that TCTP activates the anti-apoptotic function of Bcl-xL, in contrast to all other BH3-proteins. Replacing the non-conserved h1 of TCTP by that of Bax drastically increases the affinity of this hybrid for Bcl-xL, modifying its biological properties. This work reveals a novel class of BH3-proteins potentiating the anti-apoptotic function of Bcl-xL. Nature Publishing Group 2016-01-27 /pmc/articles/PMC4728560/ /pubmed/26813996 http://dx.doi.org/10.1038/srep19725 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Thébault, Stéphanie Agez, Morgane Chi, Xiaoke Stojko, Johann Cura, Vincent Telerman, Stéphanie B. Maillet, Laurent Gautier, Fabien Billas-Massobrio, Isabelle Birck, Catherine Troffer-Charlier, Nathalie Karafin, Teele Honoré, Joane Senff-Ribeiro, Andrea Montessuit, Sylvie Johnson, Christopher M. Juin, Philippe Cianférani, Sarah Martinou, Jean-Claude Andrews, David W. Amson, Robert Telerman, Adam Cavarelli, Jean |
| spellingShingle |
Thébault, Stéphanie Agez, Morgane Chi, Xiaoke Stojko, Johann Cura, Vincent Telerman, Stéphanie B. Maillet, Laurent Gautier, Fabien Billas-Massobrio, Isabelle Birck, Catherine Troffer-Charlier, Nathalie Karafin, Teele Honoré, Joane Senff-Ribeiro, Andrea Montessuit, Sylvie Johnson, Christopher M. Juin, Philippe Cianférani, Sarah Martinou, Jean-Claude Andrews, David W. Amson, Robert Telerman, Adam Cavarelli, Jean TCTP contains a BH3-like domain, which instead of inhibiting, activates Bcl-xL |
| author_facet |
Thébault, Stéphanie Agez, Morgane Chi, Xiaoke Stojko, Johann Cura, Vincent Telerman, Stéphanie B. Maillet, Laurent Gautier, Fabien Billas-Massobrio, Isabelle Birck, Catherine Troffer-Charlier, Nathalie Karafin, Teele Honoré, Joane Senff-Ribeiro, Andrea Montessuit, Sylvie Johnson, Christopher M. Juin, Philippe Cianférani, Sarah Martinou, Jean-Claude Andrews, David W. Amson, Robert Telerman, Adam Cavarelli, Jean |
| author_sort |
Thébault, Stéphanie |
| title |
TCTP contains a BH3-like domain, which instead of inhibiting, activates Bcl-xL |
| title_short |
TCTP contains a BH3-like domain, which instead of inhibiting, activates Bcl-xL |
| title_full |
TCTP contains a BH3-like domain, which instead of inhibiting, activates Bcl-xL |
| title_fullStr |
TCTP contains a BH3-like domain, which instead of inhibiting, activates Bcl-xL |
| title_full_unstemmed |
TCTP contains a BH3-like domain, which instead of inhibiting, activates Bcl-xL |
| title_sort |
tctp contains a bh3-like domain, which instead of inhibiting, activates bcl-xl |
| description |
Translationally Controlled Tumor Protein (TCTP) is anti-apoptotic, key in development and cancer, however without the typical Bcl2 family members’ structure. Here we report that TCTP contains a BH3-like domain and forms heterocomplexes with Bcl-xL. The crystal structure of a Bcl-xL deletion variant-TCTP11–31 complex reveals that TCTP refolds in a helical conformation upon binding the BH3-groove of Bcl-xL, although lacking the h1-subregion interaction. Experiments using in vitro-vivo reconstituted systems and TCTP+/− mice indicate that TCTP activates the anti-apoptotic function of Bcl-xL, in contrast to all other BH3-proteins. Replacing the non-conserved h1 of TCTP by that of Bax drastically increases the affinity of this hybrid for Bcl-xL, modifying its biological properties. This work reveals a novel class of BH3-proteins potentiating the anti-apoptotic function of Bcl-xL. |
| publisher |
Nature Publishing Group |
| publishDate |
2016 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728560/ |
| _version_ |
1613529060556668928 |