{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T16:56:50Z","timestamp":1761929810923},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,7,4]],"date-time":"2016-07-04T00:00:00Z","timestamp":1467590400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,7,4]],"date-time":"2016-07-04T00:00:00Z","timestamp":1467590400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Death Discovery"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Despite the absence of sequences showing significant similarity to any of the members of the Bcl-2 family of proteins in protozoa, experiments carried out in yeast or trypanosomatids have demonstrated that ectopic expression of some of these members alters their response to different death stimuli. Because the BH3 domain is the smallest common signature in all the proteins of this family of apoptosis regulators and also because they are essential for molecular interactions between antagonistic members, we looked for sequences with significant similarity to the BH3 motif in the<jats:italic>Leishmania infantum<\/jats:italic>genome. Among the top scoring ones, we found the MYLALQNLGDEV amino-acid stretch at the C terminus of a previously described aquaporin, now renamed as Li-BH3AQP. This motif is highly conserved in homologous proteins from other species of the<jats:italic>Leishmania<\/jats:italic>genus. The association of Li-BH3AQP with human Bcl-X<jats:sub>L<\/jats:sub>was demonstrated by both co-immunoprecipitation and yeast two-hybrid experiments. Ectopic expression of Li-BH3AQP reduced viability of HeLa cells and this deleterious effect was abrogated by the simultaneous overexpression of Bcl-X<jats:sub>L<\/jats:sub>. Although we were not able to demonstrate a reduction in parasite viability when the protein was overexpressed in<jats:italic>Leishmania<\/jats:italic>promastigotes, a prodeath effect could be observed when the parasites overexpressing Li-BH3AQP were treated with staurosporine or antimycin A. Surprisingly, these parasites were more resistant, compared with wild-type parasites, to hypotonic stress or nutrient deprivation. The prodeath activity was abolished upon replacement of two highly conserved amino acids in this BH3 domain. Taken together, these results point to Li-BH3AQP as the first non-enzymatic protein ever described in trypanosomatids that is involved in cell death.<\/jats:p>","DOI":"10.1038\/cddiscovery.2016.43","type":"journal-article","created":{"date-parts":[[2016,7,4]],"date-time":"2016-07-04T10:10:25Z","timestamp":1467627025000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["A functional BH3 domain in an aquaporin from Leishmania infantum"],"prefix":"10.1038","volume":"2","author":[{"given":"C M","family":"Genes","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"de Lucio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V M","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P A","family":"S\u00e1nchez-Murcia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E","family":"Rico","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F","family":"Gago","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N","family":"Fasel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Jim\u00e9nez-Ruiz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,7,4]]},"reference":[{"key":"BFcddiscovery201643_CR1","first-page":"285","volume":"2","author":"JC Ameisen","year":"1995","unstructured":"Ameisen JC, Idziorek T, Billaut-Mulot O, Loyens M, Tissier JP, Potentier A et al. Apoptosis in a unicellular eukaryote (Trypanosoma cruzi): implications for the evolutionary origin and role of programmed cell death in the control of cell proliferation, differentiation and survival. Cell Death Differ 1995; 2: 285\u2013300.","journal-title":"Cell Death Differ"},{"key":"BFcddiscovery201643_CR2","first-page":"229","volume":"3","author":"SC Welburn","year":"1996","unstructured":"Welburn SC, Dale C, Ellis D, Beecroft R, Pearson TW . Apoptosis in procyclic Trypanosoma brucei rhodesiense in vitro. Cell Death Differ 1996; 3: 229\u2013236.","journal-title":"Cell Death Differ"},{"key":"BFcddiscovery201643_CR3","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1007\/s00294-002-0310-2","volume":"41","author":"F Madeo","year":"2002","unstructured":"Madeo F, Engelhardt S, Herker E, Lehmann N, Maldener C, Proksch A et al. Apoptosis in yeast: a new model system with applications in cell biology and medicine. Curr Genet 2002; 41: 208\u2013216.","journal-title":"Curr Genet"},{"key":"BFcddiscovery201643_CR4","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1111\/j.1529-8817.2006.00207.x","volume":"42","author":"S Moharikar","year":"2006","unstructured":"Moharikar S, D\u2019Souza JS, Kulkarni AB, Rao BJ . Apoptotic-like cell death pathway is induced in unicellular chlorophyte Chlamydomonas reinhardtii (chlorophyceae) cells following UV irradiation: detection and functional analyses. J Phycol 2006; 42: 423\u2013433.","journal-title":"J Phycol"},{"key":"BFcddiscovery201643_CR5","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1038\/sj.cdd.4401564","volume":"12","author":"K Figarella","year":"2005","unstructured":"Figarella K, Rawer M, Uzcategui NL, Kubata BK, Lauber K, Madeo F et al. Prostaglandin D2 induces programmed cell death in Trypanosoma brucei bloodstream form. Cell Death Differ 2005; 12: 335\u2013346.","journal-title":"Cell Death Differ"},{"key":"BFcddiscovery201643_CR6","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.1038\/sj.cdd.4401071","volume":"9","author":"H Zangger","year":"2002","unstructured":"Zangger H, Mottram JC, Fasel N . Cell death in Leishmania induced by stress and differentiation: programmed cell death or necrosis? Cell Death Differ 2002; 9: 1126\u20131139.","journal-title":"Cell Death Differ"},{"key":"BFcddiscovery201643_CR7","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1007\/s10495-006-4570-z","volume":"11","author":"JF Alzate","year":"2006","unstructured":"Alzate JF, Alvarez-Barrientos A, Gonzalez VM, Jimenez-Ruiz A . Heat-induced programmed cell death in Leishmania infantum is reverted by Bcl-X(L) expression. Apoptosis 2006; 11: 161\u2013171.","journal-title":"Apoptosis"},{"key":"BFcddiscovery201643_CR8","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1016\/S0020-7519(02)00087-5","volume":"32","author":"EM Al-Olayan","year":"2002","unstructured":"Al-Olayan EM, Williams GT, Hurd H . Apoptosis in the malaria protozoan, Plasmodium berghei: a possible mechanism for limiting intensity of infection in the mosquito. Int J Parasitol 2002; 32: 1133\u20131143.","journal-title":"Int J Parasitol"},{"key":"BFcddiscovery201643_CR9","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/1756-3305-2-32","volume":"2","author":"SC Arambage","year":"2009","unstructured":"Arambage SC, Grant KM, Pardo I, Ranford-Cartwright L, Hurd H . Malaria ookinetes exhibit multiple markers for apoptosis-like programmed cell death in vitro. Parasit Vectors 2009; 2: 32.","journal-title":"Parasit Vectors"},{"key":"BFcddiscovery201643_CR10","doi-asserted-by":"publisher","first-page":"1852","DOI":"10.1086\/518253","volume":"195","author":"B Meslin","year":"2007","unstructured":"Meslin B, Barnadas C, Boni V, Latour C, De Monbrison F, Kaiser K et al. Features of apoptosis in Plasmodium falciparum erythrocytic stage through a putative role of PfMCA1 metacaspase-like protein. J Infect Dis 2007; 195: 1852\u20131859.","journal-title":"J Infect Dis"},{"key":"BFcddiscovery201643_CR11","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1016\/S0035-9203(97)90039-0","volume":"91","author":"S Picot","year":"1997","unstructured":"Picot S, Burnod J, Bracchi V, Chumpitazi BF, Ambroise-Thomas P . Apoptosis related to chloroquine sensitivity of the human malaria parasite Plasmodium falciparum. Trans R Soc Trop Med Hyg 1997; 91: 590\u2013591.","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"BFcddiscovery201643_CR12","doi-asserted-by":"publisher","first-page":"e1002320","DOI":"10.1371\/journal.ppat.1002320","volume":"7","author":"SE Reece","year":"2011","unstructured":"Reece SE, Pollitt LC, Colegrave N, Gardner A . The meaning of death: evolution and ecology of apoptosis in protozoan parasites. PLoS Pathog 2011; 7: e1002320.","journal-title":"PLoS Pathog"},{"key":"BFcddiscovery201643_CR13","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1016\/j.pt.2010.06.008","volume":"26","author":"G van Zandbergen","year":"2010","unstructured":"van Zandbergen G, Luder CG, Heussler V, Duszenko M . Programmed cell death in unicellular parasites: a prerequisite for sustained infection? Trends Parasitol 2010; 26: 477\u2013483.","journal-title":"Trends Parasitol"},{"key":"BFcddiscovery201643_CR14","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1038\/nrmicro2929","volume":"11","author":"WR Proto","year":"2012","unstructured":"Proto WR, Coombs GH, Mottram JC . Cell death in parasitic protozoa: regulated or incidental? Nat Rev Microbiol 2012; 11: 58\u201366.","journal-title":"Nat Rev Microbiol"},{"key":"BFcddiscovery201643_CR15","doi-asserted-by":"publisher","first-page":"1629","DOI":"10.1038\/cdd.2008.85","volume":"15","author":"S Bosedasgupta","year":"2008","unstructured":"Bosedasgupta S, Das BB, Sengupta S, Ganguly A, Roy A, Dey S et al. The caspase-independent algorithm of programmed cell death in Leishmania induced by baicalein: the role of LdEndoG, LdFEN-1 and LdTatD as a DNA 'degradesome'. Cell Death Differ 2008; 15: 1629\u20131640.","journal-title":"Cell Death Differ"},{"key":"BFcddiscovery201643_CR16","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1242\/jcs.014050","volume":"121","author":"S Gannavaram","year":"2008","unstructured":"Gannavaram S, Vedvyas C, Debrabant A . Conservation of the pro-apoptotic nuclease activity of endonuclease G in unicellular trypanosomatid parasites. J Cell Sci 2008; 121: 99\u2013109.","journal-title":"J Cell Sci"},{"key":"BFcddiscovery201643_CR17","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.molbiopara.2008.09.007","volume":"163","author":"E Rico","year":"2009","unstructured":"Rico E, Alzate JF, Arias AA, Moreno D, Clos J, Gago F et al. Leishmania infantum expresses a mitochondrial nuclease homologous to EndoG that migrates to the nucleus in response to an apoptotic stimulus. Mol Biochem Parasitol 2009; 163: 28\u201338.","journal-title":"Mol Biochem Parasitol"},{"key":"BFcddiscovery201643_CR18","doi-asserted-by":"publisher","first-page":"1745","DOI":"10.1128\/EC.00123-07","volume":"6","author":"N Lee","year":"2007","unstructured":"Lee N, Gannavaram S, Selvapandiyan A, Debrabant A . Characterization of metacaspases with trypsin-like activity and their putative role in programmed cell death in the protozoan parasite Leishmania. Eukaryot Cell 2007; 6: 1745\u20131757.","journal-title":"Eukaryot Cell"},{"key":"BFcddiscovery201643_CR19","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1111\/j.1365-2958.2010.07443.x","volume":"79","author":"H Zalila","year":"2011","unstructured":"Zalila H, Gonzalez IJ, El-Fadili AK, Delgado MB, Desponds C, Schaff C et al. Processing of metacaspase into a cytoplasmic catalytic domain mediating cell death in Leishmania major. Mol Microbiol 2011; 79: 222\u2013239.","journal-title":"Mol Microbiol"},{"key":"BFcddiscovery201643_CR20","doi-asserted-by":"publisher","first-page":"e1933","DOI":"10.1038\/cddis.2015.288","volume":"6","author":"M Casanova","year":"2015","unstructured":"Casanova M, Gonzalez IJ, Sprissler C, Zalila H, Dacher M, Basmaciyan L et al. Implication of different domains of the Leishmania major metacaspase in cell death and autophagy. Cell Death Dis 2015; 6: e1933.","journal-title":"Cell Death Dis"},{"key":"BFcddiscovery201643_CR21","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1016\/j.yexcr.2010.12.001","volume":"317","author":"RD Silva","year":"2011","unstructured":"Silva RD, Manon S, Goncalves J, Saraiva L, Corte-Real M . Modulation of Bax mitochondrial insertion and induced cell death in yeast by mammalian protein kinase Calpha. Exp Cell Res 2011; 317: 781\u2013790.","journal-title":"Exp Cell Res"},{"key":"BFcddiscovery201643_CR22","doi-asserted-by":"publisher","first-page":"44870","DOI":"10.1074\/jbc.M204888200","volume":"277","author":"MG Vander Heiden","year":"2002","unstructured":"Vander Heiden MG, Choy JS, VanderWeele DJ, Brace JL, Harris MH, Bauer DE et al. Bcl-x(L) complements Saccharomyces cerevisiae genes that facilitate the switch from glycolytic to oxidative metabolism. J Biol Chem 2002; 277: 44870\u201344876.","journal-title":"J Biol Chem"},{"key":"BFcddiscovery201643_CR23","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1038\/sj.cdd.4400951","volume":"9","author":"D Arnoult","year":"2002","unstructured":"Arnoult D, Akarid K, Grodet A, Petit PX, Estaquier J, Ameisen JC . On the evolution of programmed cell death: apoptosis of the unicellular eukaryote Leishmania major involves cysteine proteinase activation and mitochondrion permeabilization. Cell Death Differ 2002; 9: 65\u201381.","journal-title":"Cell Death Differ"},{"key":"BFcddiscovery201643_CR24","doi-asserted-by":"publisher","first-page":"2779","DOI":"10.1038\/emboj.2011.197","volume":"30","author":"S Buttner","year":"2011","unstructured":"Buttner S, Ruli D, Vogtle FN, Galluzzi L, Moitzi B, Eisenberg T et al. A yeast BH3-only protein mediates the mitochondrial pathway of apoptosis. EMBO J 2011; 30: 2779\u20132792.","journal-title":"EMBO J"},{"key":"BFcddiscovery201643_CR25","doi-asserted-by":"publisher","first-page":"e24820","DOI":"10.1371\/journal.pone.0024820","volume":"6","author":"N Biyani","year":"2011","unstructured":"Biyani N, Mandal S, Seth C, Saint M, Natarajan K, Ghosh I et al. Characterization of Leishmania donovani aquaporins shows presence of subcellular aquaporins similar to tonoplast intrinsic proteins of plants. PLoS One 2011; 6: e24820.","journal-title":"PLoS One"},{"key":"BFcddiscovery201643_CR26","doi-asserted-by":"publisher","first-page":"6097","DOI":"10.1093\/nar\/18.20.6097","volume":"18","author":"TD Schneider","year":"1990","unstructured":"Schneider TD, Stephens RM . Sequence logos: a new way to display consensus sequences. Nucleic Acids Res 1990; 18: 6097\u20136100.","journal-title":"Nucleic Acids Res"},{"key":"BFcddiscovery201643_CR27","doi-asserted-by":"crossref","unstructured":"PROSITE. Available at: http:\/\/prosite.expasy.org\/PS01259. Last accessed date 1 May 2016.","DOI":"10.1002\/9783527678679.dg10087"},{"key":"BFcddiscovery201643_CR28","doi-asserted-by":"publisher","first-page":"e1000130","DOI":"10.1371\/journal.pbio.1000130","volume":"7","author":"G Fischer","year":"2009","unstructured":"Fischer G, Kosinska-Eriksson U, Aponte-Santamar\u00eda C, Palmgren M, Geijer C, Hedfalk K et al. Crystal structure of a yeast aquaporin at 1.15\u2009\u00c5 reveals a novel gating mechanism. PLoS Biol 2009; 7: e1000130.","journal-title":"PLoS Biol"},{"key":"BFcddiscovery201643_CR29","doi-asserted-by":"publisher","first-page":"18932","DOI":"10.1073\/pnas.0509469102","volume":"102","author":"JK Lee","year":"2005","unstructured":"Lee JK, Kozono D, Remis J, Kitagawa Y, Agre P, Stroud RM . Structural basis for conductance by the archaeal aquaporin AqpM at 1.68A. Proc Natl Acad Sci USA 2005; 102: 18932\u201318937.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFcddiscovery201643_CR30","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1111\/j.1742-4658.2010.07993.x","volume":"278","author":"D Wree","year":"2011","unstructured":"Wree D, Wu B, Zeuthen T, Beitz E . Requirement for asparagine in the aquaporin NPA sequence signature motifs for cation exclusion. FEBS J 2011; 278: 740\u2013748.","journal-title":"FEBS J"},{"key":"BFcddiscovery201643_CR31","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1038\/nsmb.1431","volume":"15","author":"ZE Newby","year":"2008","unstructured":"Newby ZE, O'Connell J III, Robles-Colmenares Y, Khademi S, Miercke LJ, Stroud RM . Crystal structure of the aquaglyceroporin PfAQP from the malarial parasite Plasmodium falciparum. Nat Struct Mol Biol 2008; 15: 619\u2013625.","journal-title":"Nat Struct Mol Biol"},{"key":"BFcddiscovery201643_CR32","unstructured":"Gago F . Available at: http:\/\/farmamol.uah.es. Last accessed date 1 May 2016."},{"key":"BFcddiscovery201643_CR33","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1021\/jm00145a002","volume":"28","author":"PJ Goodford","year":"1985","unstructured":"Goodford PJ . A computational procedure for determining energetically favorable binding sites on biologically important macromolecules. J Med Chem 1985; 28: 849\u2013857.","journal-title":"J Med Chem"},{"key":"BFcddiscovery201643_CR34","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/S1074-7613(03)00234-6","volume":"19","author":"X Liu","year":"2003","unstructured":"Liu X, Dai S, Zhu Y, Marrack P, Kappler JW . The structure of a Bcl-xL\/Bim fragment complex: implications for Bim function. Immunity 2003; 19: 341\u2013352.","journal-title":"Immunity"},{"key":"BFcddiscovery201643_CR35","doi-asserted-by":"publisher","first-page":"1686","DOI":"10.1093\/emboj\/16.7.1686","volume":"16","author":"N Inohara","year":"1997","unstructured":"Inohara N, Ding L, Chen S, Nunez G . Harakiri, a novel regulator of cell death, encodes a protein that activates apoptosis and interacts selectively with survival-promoting proteins Bcl-2 and Bcl-X(L). EMBO J 1997; 16: 1686\u20131694.","journal-title":"EMBO J"},{"key":"BFcddiscovery201643_CR36","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.tcb.2012.10.010","volume":"23","author":"A Aouacheria","year":"2013","unstructured":"Aouacheria A, Rech de Laval V, Combet C, Hardwick JM . Evolution of Bcl-2 homology motifs: homology versus homoplasy. Trends Cell Biol 2013; 23: 103\u2013111.","journal-title":"Trends Cell Biol"},{"key":"BFcddiscovery201643_CR37","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1038\/sj.cdd.4401987","volume":"13","author":"S Zinkel","year":"2006","unstructured":"Zinkel S, Gross A, Yang E . BCL2 family in DNA damage and cell cycle control. Cell Death Differ 2006; 13: 1351\u20131359.","journal-title":"Cell Death Differ"},{"key":"BFcddiscovery201643_CR38","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1016\/j.cell.2005.06.022","volume":"122","author":"SS Zinkel","year":"2005","unstructured":"Zinkel SS, Hurov KE, Ong C, Abtahi FM, Gross A, Korsmeyer SJ . A role for proapoptotic BID in the DNA-damage response. Cell 2005; 122: 579\u2013591.","journal-title":"Cell"},{"key":"BFcddiscovery201643_CR39","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1016\/j.cell.2005.06.014","volume":"122","author":"I Kamer","year":"2005","unstructured":"Kamer I, Sarig R, Zaltsman Y, Niv H, Oberkovitz G, Regev L et al. Proapoptotic BID is an ATM effector in the DNA-damage response. Cell 2005; 122: 593\u2013603.","journal-title":"Cell"},{"key":"BFcddiscovery201643_CR40","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1089\/ars.2005.7.508","volume":"7","author":"AJ Kowaltowski","year":"2005","unstructured":"Kowaltowski AJ, Fiskum G . Redox mechanisms of cytoprotection by Bcl-2. Antioxid Redox Signal 2005; 7: 508\u2013514.","journal-title":"Antioxid Redox Signal"},{"key":"BFcddiscovery201643_CR41","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1038\/nature01825","volume":"424","author":"NN Danial","year":"2003","unstructured":"Danial NN, Gramm CF, Scorrano L, Zhang CY, Krauss S, Ranger AM et al. BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis. Nature 2003; 424: 952\u2013956.","journal-title":"Nature"},{"key":"BFcddiscovery201643_CR42","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.tcb.2007.10.003","volume":"18","author":"C Hetz","year":"2008","unstructured":"Hetz C, Glimcher L . The daily job of night killers: alternative roles of the BCL-2 family in organelle physiology. Trends Cell Biol 2008; 18: 38\u201344.","journal-title":"Trends Cell Biol"},{"key":"BFcddiscovery201643_CR43","doi-asserted-by":"publisher","first-page":"E209","DOI":"10.1038\/70237","volume":"1","author":"MG Vander Heiden","year":"1999","unstructured":"Vander Heiden MG, Thompson CB . Bcl-2 proteins: regulators of apoptosis or of mitochondrial homeostasis? Nat Cell Biol 1999; 1: E209\u2013E216.","journal-title":"Nat Cell Biol"},{"key":"BFcddiscovery201643_CR44","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1016\/j.tcb.2012.03.005","volume":"22","author":"JM Hardwick","year":"2012","unstructured":"Hardwick JM, Chen YB, Jonas EA . Multipolar functions of BCL-2 proteins link energetics to apoptosis. Trends Cell Biol 2012; 22: 318\u2013328.","journal-title":"Trends Cell Biol"},{"key":"BFcddiscovery201643_CR45","doi-asserted-by":"publisher","first-page":"5991","DOI":"10.1074\/jbc.M114.624650","volume":"290","author":"S Neidel","year":"2015","unstructured":"Neidel S, Maluquer de Motes C, Mansur DS, Strnadova P, Smith GL, Graham SC . Vaccinia virus protein A49 is an unexpected member of the B-cell Lymphoma (Bcl)-2 protein family. J Biol Chem 2015; 290: 5991\u20136002.","journal-title":"J Biol Chem"},{"key":"BFcddiscovery201643_CR46","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1189\/jlb.0611326","volume":"91","author":"U Lambertz","year":"2012","unstructured":"Lambertz U, Silverman JM, Nandan D, McMaster WR, Clos J, Foster LJ et al. Secreted virulence factors and immune evasion in visceral leishmaniasis. J Leukoc Biol 2012; 91: 887\u2013899.","journal-title":"J Leukoc Biol"},{"key":"BFcddiscovery201643_CR47","doi-asserted-by":"publisher","first-page":"2947","DOI":"10.1093\/bioinformatics\/btm404","volume":"23","author":"MA Larkin","year":"2007","unstructured":"Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H et al. Clustal W and Clustal X version 2.0. Bioinformatics 2007; 23: 2947\u20132948.","journal-title":"Bioinformatics"},{"key":"BFcddiscovery201643_CR48","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1038\/nprot.2015.053","volume":"10","author":"LA Kelley","year":"2015","unstructured":"Kelley LA, Mezulis S, Yates CM, Wass MN, Sternberg MJE . The Phyre2 web portal for protein modeling, prediction and analysis. Nat Protocols 2015; 10: 845\u2013858.","journal-title":"Nat Protocols"},{"key":"BFcddiscovery201643_CR49","doi-asserted-by":"publisher","first-page":"W252","DOI":"10.1093\/nar\/gku340","volume":"42","author":"M Biasini","year":"2014","unstructured":"Biasini M, Bienert S, Waterhouse A, Arnold K, Studer G, Schmidt T et al. SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information. Nucleic Acids Res 2014; 42: W252\u2013W258.","journal-title":"Nucleic Acids Res"},{"key":"BFcddiscovery201643_CR50","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1093\/beheco\/ark016","volume":"17","author":"GD Ruxton","year":"2006","unstructured":"Ruxton GD . The unequal variance t-test is an underused alternative to Student's t-test and the Mann\u2013Whitney U test. Behav Ecol 2006; 17: 688\u2013690.","journal-title":"Behav Ecol"},{"key":"BFcddiscovery201643_CR51","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1080\/00031305.1992.10475839","volume":"46","author":"BK Moser","year":"1992","unstructured":"Moser BK, Stevens GR . Homogeneity of variance in the two-sample means test. Am Stat 1992; 46: 19\u201321.","journal-title":"Am Stat"}],"container-title":["Cell Death Discovery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/cddiscovery201643.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/cddiscovery201643","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/cddiscovery201643.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T02:03:39Z","timestamp":1718676219000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/cddiscovery201643"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,7,4]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,12,12]]}},"alternative-id":["BFcddiscovery201643"],"URL":"https:\/\/doi.org\/10.1038\/cddiscovery.2016.43","relation":{},"ISSN":["2058-7716"],"issn-type":[{"type":"electronic","value":"2058-7716"}],"subject":[],"published":{"date-parts":[[2016,7,4]]},"assertion":[{"value":"10 May 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 May 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 July 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"16043"}}