TY - JOUR
T1 - TCTP contains a BH3-like domain, which instead of inhibiting, activates Bcl-xL
AU - Thébault, Stéphanie
AU - Agez, Morgane
AU - Chi, Xiaoke
AU - Stojko, Johann
AU - Cura, Vincent
AU - Telerman, Stéphanie B
AU - Maillet, Laurent
AU - Gautier, Fabien
AU - Billas-Massobrio, Isabelle
AU - Birck, Catherine
AU - Troffer-Charlier, Nathalie
AU - Karafin, Teele
AU - Honoré, Joane
AU - Senff-Ribeiro, Andrea
AU - Montessuit, Sylvie
AU - Johnson, Christopher M
AU - Juin, Philippe
AU - Cianférani, Sarah
AU - Martinou, Jean-Claude
AU - Andrews, David W
AU - Amson, Robert
AU - Telerman, Adam
AU - Cavarelli, Jean
PY - 2016/1/27
Y1 - 2016/1/27
N2 - 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.
AB - 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.
U2 - 10.1038/srep19725
DO - 10.1038/srep19725
M3 - Article
C2 - 26813996
SN - 2045-2322
VL - 6
JO - Scientific Reports
JF - Scientific Reports
M1 - 19725
ER -