TCTP contains a BH3-like domain, which instead of inhibiting, activates Bcl-xL

Stéphanie Thébault, Morgane Agez, Xiaoke Chi, Johann Stojko, Vincent Cura, Stéphanie B Telerman, Laurent Maillet, Fabien Gautier, Isabelle Billas-Massobrio, Catherine Birck, Nathalie Troffer-Charlier, Teele Karafin, Joane Honoré, Andrea Senff-Ribeiro, Sylvie Montessuit, Christopher M Johnson, Philippe Juin, Sarah Cianférani, Jean-Claude Martinou, David W AndrewsRobert Amson, Adam Telerman, Jean Cavarelli

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42 Citations (Scopus)
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Abstract

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.

Original languageEnglish
Article number19725
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 27 Jan 2016

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