title: Bax transmembrane domain interacts with prosurvival Bcl-2 proteins in biological membranes.
abstract: The Bcl-2 (B-cell lymphoma 2) protein Bax (Bcl-2 associated X, apoptosis regulator) can commit cells to apoptosis via outer mitochondrial membrane permeabilization. Bax activity is controlled in healthy cells by prosurvival Bcl-2 proteins. C-terminal Bax transmembrane domain interactions were implicated recently in Bax pore formation. Here, we show that the isolated transmembrane domains of Bax, Bcl-xL(B-cell lymphoma-extra large), and Bcl-2 can mediate interactions between Bax and prosurvival proteins inside the membrane in the absence of apoptotic stimuli. Bcl-2 protein transmembrane domains specifically homooligomerize and heterooligomerize in bacterial and mitochondrial membranes. Their interactions participate in the regulation of Bcl-2 proteins, thus modulating apoptotic activity. Our results suggest that interactions between the transmembrane domains of Bax and antiapoptotic Bcl-2 proteins represent a previously unappreciated level of apoptosis regulation.
authors.affiliation: Laboratory of Peptide and Protein Chemistry, Centro de Investigación Príncipe Felipe, E-46012 Valencia, Spain.|Institute for Biochemistry and Molecular Biology, University of Freiburg, 79104 Freiburg, Germany.|Departament de Bioquímica i Biologia Molecular, Estructura de Recerca Interdisciplinar en Biotecnología i Biomedicina, Universitat de València, 46100 Burjassot, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Andreu-Fernández
authors.affiliation: Laboratory of Peptide and Protein Chemistry, Centro de Investigación Príncipe Felipe, E-46012 Valencia, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Sancho
authors.affiliation: Laboratory of Peptide and Protein Chemistry, Centro de Investigación Príncipe Felipe, E-46012 Valencia, Spain.
authors.forename: Ainhoa
authors.initials: A
authors.lastname: Genovés
authors.affiliation: Laboratory of Peptide and Protein Chemistry, Centro de Investigación Príncipe Felipe, E-46012 Valencia, Spain.
authors.forename: Estefanía
authors.initials: E
authors.lastname: Lucendo
authors.affiliation: Institute for Biochemistry and Molecular Biology, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Todt
authors.affiliation: Institute for Biochemistry and Molecular Biology, University of Freiburg, 79104 Freiburg, Germany.|Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Lauterwasser
authors.affiliation: Institute for Biochemistry and Molecular Biology, University of Freiburg, 79104 Freiburg, Germany.|Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Funk
authors.affiliation: Department of Biochemistry/Biotechnology, Martin Luther University Halle-Wittenberg, 06120 Halle, Germany.
authors.forename: Günther
authors.initials: G
authors.lastname: Jahreis
authors.affiliation: Laboratory of Peptide and Protein Chemistry, Centro de Investigación Príncipe Felipe, E-46012 Valencia, Spain.|Instituto de Biomedicina de Valencia, Instituto de Biomedicina de Valencia-Consejo Superior de Investigaciones Científicas, 46010 Valencia, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Pérez-Payá
authors.affiliation: Departament de Bioquímica i Biologia Molecular, Estructura de Recerca Interdisciplinar en Biotecnología i Biomedicina, Universitat de València, 46100 Burjassot, Spain; morzaez@cipf.es Ismael.Mingarro@uv.es frank.edlich@biochemie.uni-freiburg.de.
authors.forename: Ismael
authors.initials: I
authors.lastname: Mingarro
authors.affiliation: Institute for Biochemistry and Molecular Biology, University of Freiburg, 79104 Freiburg, Germany; morzaez@cipf.es Ismael.Mingarro@uv.es frank.edlich@biochemie.uni-freiburg.de.|BIOSS, Centre for Biological Signaling Studies, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Edlich
authors.affiliation: Laboratory of Peptide and Protein Chemistry, Centro de Investigación Príncipe Felipe, E-46012 Valencia, Spain; morzaez@cipf.es Ismael.Mingarro@uv.es frank.edlich@biochemie.uni-freiburg.de.
authors.forename: Mar
authors.initials: M
authors.lastname: Orzáez
mesh_terms: D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism; D045325:HCT116 Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D000072417:Protein Domains / Q000502:physiology; D051028:bcl-2-Associated X Protein / Q000378:metabolism*; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D008565:Membrane Proteins; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
keywords: Bcl-2; apoptosis; mitochondria; oligomerization; transmembrane