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.

• Authors: 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 Andrews, Robert Amson, Adam Telerman, Jean Cavarelli
• Journal: Scientific reports (Sci Rep) Vol. 6 Pg. 19725 (Jan 27 2016) ISSN: 2045-2322 [Electronic] England
• PMID: 26813996 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BH3 Interacting Domain Death Agonist Protein
• Biomarkers, Tumor
• Multiprotein Complexes
• Tpt1 protein, mouse
• Tumor Protein, Translationally-Controlled 1
• bcl-2-Associated X Protein
• bcl-X Protein

Topics

• Amino Acid Sequence
• Animals
• Apoptosis
• BH3 Interacting Domain Death Agonist Protein (metabolism)
• Biomarkers, Tumor (chemistry, metabolism)
• Cell Membrane Permeability
• Mice
• Models, Molecular
• Multiprotein Complexes (metabolism)
• Protein Binding
• Protein Conformation
• Protein Interaction Domains and Motifs
• Protein Multimerization
• Tumor Protein, Translationally-Controlled 1
• bcl-2-Associated X Protein (metabolism)
• bcl-X Protein (chemistry, metabolism)