title: 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.affiliation: 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.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Thébault
authors.affiliation: 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.|Institut Gustave Roussy, Unité Inserm U981, Bâtiment B2M, 114 rue Édouard-Vaillant, 94805 Villejuif, France.
authors.forename: Morgane
authors.initials: M
authors.lastname: Agez
authors.affiliation: 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.
authors.forename: Xiaoke
authors.initials: X
authors.lastname: Chi
authors.affiliation: Laboratoire de Spectrométrie de Masse BioOrganique (LSMBO), IPHC-DSA, Université de Strasbourg, CNRS, UMR7178, 25 rue Becquerel, 67087 Strasbourg, France.
authors.forename: Johann
authors.initials: J
authors.lastname: Stojko
authors.affiliation: 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.
authors.forename: Vincent
authors.initials: V
authors.lastname: Cura
authors.affiliation: 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.
authors.forename: Stéphanie B
authors.initials: SB
authors.lastname: Telerman
authors.affiliation: 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.
authors.forename: Laurent
authors.initials: L
authors.lastname: Maillet
authors.affiliation: 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.
authors.forename: Fabien
authors.initials: F
authors.lastname: Gautier
authors.affiliation: 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.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Billas-Massobrio
authors.affiliation: 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.
authors.forename: Catherine
authors.initials: C
authors.lastname: Birck
authors.affiliation: 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.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Troffer-Charlier
authors.affiliation: 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.
authors.forename: Teele
authors.initials: T
authors.lastname: Karafin
authors.affiliation: Institut Gustave Roussy, Unité Inserm U981, Bâtiment B2M, 114 rue Édouard-Vaillant, 94805 Villejuif, France.
authors.forename: Joane
authors.initials: J
authors.lastname: Honoré
authors.affiliation: 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.
authors.forename: Andrea
authors.initials: A
authors.lastname: Senff-Ribeiro
authors.affiliation: Department of Cell Biology, University of Geneva, 30, quai Ansermet, 1211 Geneva 4, Switzerland.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Montessuit
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Johnson
authors.affiliation: 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.
authors.forename: Philippe
authors.initials: P
authors.lastname: Juin
authors.affiliation: Laboratoire de Spectrométrie de Masse BioOrganique (LSMBO), IPHC-DSA, Université de Strasbourg, CNRS, UMR7178, 25 rue Becquerel, 67087 Strasbourg, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Cianférani
authors.affiliation: Department of Cell Biology, University of Geneva, 30, quai Ansermet, 1211 Geneva 4, Switzerland.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Martinou
authors.affiliation: 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.
authors.forename: David W
authors.initials: DW
authors.lastname: Andrews
authors.affiliation: 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.
authors.forename: Robert
authors.initials: R
authors.lastname: Amson
authors.affiliation: 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.
authors.forename: Adam
authors.initials: A
authors.lastname: Telerman
authors.affiliation: 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.
authors.forename: Jean
authors.initials: J
authors.lastname: Cavarelli
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000737:chemistry / Q000378:metabolism*; D002463:Cell Membrane Permeability; D051379:Mice; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D000090324:Tumor Protein, Translationally-Controlled 1; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000737:chemistry / Q000378:metabolism*
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; D014408:Biomarkers, Tumor; D046912:Multiprotein Complexes; C000715648:Tpt1 protein, mouse; D000090324:Tumor Protein, Translationally-Controlled 1; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
references.citation: Cell. 1995 Jan 27;80(2):285-91
references.pmid: 7834748
references.citation: Mol Cell. 2007 Mar 23;25(6):933-42
references.pmid: 17386268
references.citation: Mol Cell. 2012 Mar 30;45(6):754-63
references.pmid: 22464442
references.citation: PLoS Biol. 2008 Jun 10;6(6):e147
references.pmid: 18547146
references.citation: Biochem J. 2011 Sep 1;438(2):291-301
references.pmid: 21639858
references.citation: J Biol Chem. 2004 Sep 24;279(39):40868-75
references.pmid: 15262975
references.citation: ACS Chem Biol. 2013 Feb 15;8(2):297-302
references.pmid: 23151250
references.citation: Mol Cell. 2000 Dec;6(6):1389-99
references.pmid: 11163212
references.citation: Folia Histochem Cytobiol. 2012;50(3):358-67
references.pmid: 23042265
references.citation: Yeast. 1997 Dec;13(16):1519-34
references.pmid: 9509572
references.citation: Nat Rev Cancer. 2009 Mar;9(3):206-16
references.pmid: 19180095
references.citation: Annu Rev Genet. 2013;47:601-23
references.pmid: 24274755
references.citation: J Biol Chem. 2014 Dec 26;289(52):36001-17
references.pmid: 25371206
references.citation: Nat Struct Biol. 2001 Aug;8(8):701-4
references.pmid: 11473261
references.citation: Mol Biol Cell. 2007 Jul;18(7):2525-32
references.pmid: 17475776
references.citation: Nat Chem Biol. 2013 Mar;9(3):163-8
references.pmid: 23340338
references.citation: Oncogene. 2005 Jul 14;24(30):4778-88
references.pmid: 15870695
references.citation: Nat Struct Mol Biol. 2014 Jun;21(6):535-43
references.pmid: 24814347
references.citation: Mol Cell Biol. 2005 Apr;25(8):3117-26
references.pmid: 15798198
references.citation: EMBO J. 1999 Feb 1;18(3):632-43
references.pmid: 9927423
references.citation: J Mol Biol. 2007 Sep 7;372(1):223-35
references.pmid: 17659302
references.citation: Science. 1995 Aug 4;269(5224):688-90
references.pmid: 7542803
references.citation: J Thromb Haemost. 2010 Feb;8(2):221-7
references.pmid: 19912518
references.citation: Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14976-81
references.pmid: 12399545
references.citation: Proc Natl Acad Sci U S A. 2004 Oct 26;101(43):15364-9
references.pmid: 15489264
references.citation: Curr Opin Oncol. 2013 Jan;25(1):59-65
references.pmid: 23165143
references.citation: Science. 2004 Feb 13;303(5660):1010-4
references.pmid: 14963330
references.citation: J Biol Chem. 2002 Oct 4;277(40):37430-8
references.pmid: 12149273
references.citation: Nat Med. 2012 Jan;18(1):91-9
references.pmid: 22157679
references.citation: Protein Sci. 2000 Dec;9(12):2528-34
references.pmid: 11206074
references.citation: Biochem Res Int. 2012;2012:541906
references.pmid: 22655198
references.citation: Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21
references.pmid: 20124702
references.citation: Cell. 2010 Sep 17;142(6):889-901
references.pmid: 20850011
references.citation: Mol Cell Biol. 2000 Feb;20(3):929-35
references.pmid: 10629050
references.citation: Carcinogenesis. 2009 Apr;30(4):555-65
references.pmid: 19168579
references.citation: Cell Death Dis. 2014;5:e1291
references.pmid: 24922075
references.citation: Nat Chem Biol. 2015 Jan;11(1):16-8
references.pmid: 25402770
references.citation: Nat Rev Cancer. 2013 Jul;13(7):455-65
references.pmid: 23783119
references.citation: Cell. 2013 Jan 31;152(3):519-31
references.pmid: 23374347
references.citation: Cell. 2012 Jul 20;150(2):291-303
references.pmid: 22817892
references.citation: Anal Biochem. 2013 Apr 1;435(1):47-53
references.pmid: 23256924
references.citation: Trends Cell Biol. 2013 Jan;23(1):37-46
references.pmid: 23122550
references.citation: Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2210-21
references.pmid: 15572774
references.citation: Science. 1984 Nov 30;226(4678):1097-9
references.pmid: 6093263
references.citation: Biomaterials. 2011 Aug;32(22):5262-8
references.pmid: 21565400
references.citation: Biomaterials. 2011 Jan;32(1):222-30
references.pmid: 20863558
references.citation: Anal Biochem. 2005 Aug 15;343(2):313-21
references.pmid: 15993367
references.citation: Sci Rep. 2015;5:8061
references.pmid: 25622969
references.citation: J Biol Chem. 2007 Apr 27;282(17):13123-32
references.pmid: 17337444
references.citation: Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
references.pmid: 15572765
references.citation: Cell. 1993 Oct 22;75(2):229-40
references.pmid: 8402909
references.citation: Curr Biol. 2007 May 1;17(9):801-7
references.pmid: 17442571
references.citation: Cell Death Differ. 2008 Aug;15(8):1211-20
references.pmid: 18274553
references.citation: Mol Pharm. 2015 Jan 5;12(1):194-203
references.pmid: 25423047
references.citation: Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):125-32
references.pmid: 20124692
references.citation: Trends Biochem Sci. 2014 Mar;39(3):101-11
references.pmid: 24503222
references.citation: Cell. 1991 Nov 29;67(5):879-88
references.pmid: 1835668
references.citation: Cell. 1991 Nov 29;67(5):889-99
references.pmid: 1959134
references.citation: Science. 1997 Feb 14;275(5302):983-6
references.pmid: 9020082
references.citation: Nat Rev Mol Cell Biol. 2008 Jan;9(1):47-59
references.pmid: 18097445