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

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.
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Submitted on : Monday, June 20, 2016 - 12:33:13 PM
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Stéphanie Thébault, Morgane Agez, Xiaoke Chi, Johann Stojko, Vincent Cura, et al.. TCTP contains a BH3-like domain, which instead of inhibiting, activates Bcl-xL.. Scientific Reports, Nature Publishing Group, 2015, 6 (1), pp.19725. ⟨10.1038/srep19725⟩. ⟨inserm-01334033⟩



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