TCTP contains a BH3-like domain, which instead of inhibiting, activates Bcl-xL.
Fiche publication
Date publication
janvier 2016
Journal
Scientific reports
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BIRCK Catherine, Pr CAVARELLI Jean, Dr CIANFERANI Sarah, Dr BILLAS Isabelle
Tous les auteurs :
Thébault S, Agez M, Chi X, Stojko J, Cura V, Telerman SB, Maillet L, Gautier F, Billas-Massobrio I, Birck C, Troffer-Charlier N, Karafin T, Honoré J, Senff-Ribeiro A, Montessuit S, Johnson CM, Juin P, Cianférani S, Martinou JC, Andrews DW, Amson R, Telerman A, Cavarelli J
Lien Pubmed
Résumé
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.
Mots clés
Amino Acid Sequence, Animals, Apoptosis, BH3 Interacting Domain Death Agonist Protein, metabolism, Biomarkers, Tumor, chemistry, Cell Membrane Permeability, Mice, Models, Molecular, Multiprotein Complexes, metabolism, Protein Binding, Protein Conformation, Protein Interaction Domains and Motifs, Protein Multimerization, bcl-2-Associated X Protein, metabolism, bcl-X Protein, chemistry
Référence
Sci Rep. 2016 Jan;6:19725