Afficher la couverture 'TCTP contains a BH3-like domain, which instead of inhibiting, activates Bcl-xL. | Thébault, Stéphanie' en grand format
/5

0 avis

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

Archive ouverte

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

Edité par CCSD ; Nature Publishing Group -

International audience. 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.

Suggestions

Du même auteur

TCTP regulates genotoxic stress and tumorigenicity via intercellular vesicular signaling

Archive ouverte | Amson, Robert | CCSD

International audience. Oncogenic intercellular signaling is regulated by extracellular vesicles (EVs), but the underlying mechanisms remain mostly unclear. Since TCTP (translationally controlled tumor protein) is a...

Constitutive p53 heightens mitochondrial apoptotic priming and favors cell death induction by BH3 mimetic inhibitors of BCL-xL.

Archive ouverte | Le Pen, J | CCSD

International audience. Proapoptotic molecules directly targeting the BCL-2 family network are promising anticancer therapeutics, but an understanding of the cellular stress signals that render them effective is sti...

Acetylation of translationally controlled tumor protein promotes its degradation through chaperone-mediated autophagy

Archive ouverte | Bonhoure, Anne | CCSD

International audience. Translationally controlled tumor protein (Tpt1/TCTP) is a multi-functional cytosolic protein whose cellular levels are finely tuned. TCTP regulates protein behavior by favoring stabilization ...

Chargement des enrichissements...