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Sci Rep. 2016 Jan 27;6:19725. doi: 10.1038/srep19725.

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

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Département de Biologie Structurale Intégrative, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg, CNRS UMR 7104, INSERM U964, 1 rue Laurent Fries, BP 10142, F-67404 Illkirch, France.
CNRS-UMR 8113, LBPA, École Normale Supérieure, 61 avenue du Président Wilson, 94235 Cachan, France.
Institut Gustave Roussy, Unité Inserm U981, Bâtiment B2M, 114 rue Édouard-Vaillant, 94805 Villejuif, France.
Sunnybrook Research Institute and Departments of Biochemistry and Medical Biophysics, University of Toronto, 2075 Bayview Ave., Toronto, Ontario, M4N 3M5, Canada.
Department of Chemistry and Chemical Biology, McMaster University, 1280 Main St. W. Hamilton, Ontario, L8N 3Z5, Canada.
Laboratoire de Spectrométrie de Masse BioOrganique (LSMBO), IPHC-DSA, Université de Strasbourg, CNRS, UMR7178, 25 rue Becquerel, 67087 Strasbourg, France.
King's College London Centre for Stem Cells and Regenerative Medicine, Tower Wing, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK.
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK.
Center for Cancer Research Nantes-Angers, UMR 892 Inserm - 6299 CNRS/Université de Nantes, IRS-UN, 8 Quai Moncousu - BP 70721, 44007 Nantes Cedex 1.
Institut de Cancérologie de l'Ouest, Centre René Gauducheau Bd Jacques Monod, 44805 Saint Herblain-Nantes cedex.
Department of Cell Biology, University of Geneva, 30, quai Ansermet, 1211 Geneva 4, Switzerland.


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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