{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T18:50:37Z","timestamp":1784314237695,"version":"3.55.0"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,1,23]],"date-time":"2017-01-23T00:00:00Z","timestamp":1485129600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,1,23]],"date-time":"2017-01-23T00:00:00Z","timestamp":1485129600000},"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":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>c-Myb is a transcription factor that plays a key role in cell proliferation, differentiation, and apoptosis. It has been reported that c-Myb is expressed within the chicken otic placode, but whether c-Myb exists in the mammalian cochlea, and how it exerts its effects, has not been explored yet. Here, we investigated the expression of c-Myb in the postnatal mouse cochlea and HEI-OC1 cells and found that c-Myb was expressed in the hair cells (HCs) of mouse cochlea as well as in cultured HEI-OC1 cells. Next, we demonstrated that c-Myb expression was decreased in response to neomycin treatment in both cochlear HCs and HEI-OC1 cells, suggesting an otoprotective role for c-Myb. We then knocked down c-Myb expression with shRNA transfection in HEI-OC1 cells and found that c-Myb knockdown decreased cell viability, increased expression of pro-apoptotic factors, and enhanced cell apoptosis after neomycin insult. Mechanistic studies revealed that c-Myb knockdown increased cellular levels of reactive oxygen species and decreased Bcl-2 expression, both of which are likely to be responsible for the increased sensitivity of c-Myb knockdown cells to neomycin. This study provides evidence that c-Myb might serve as a new target for the prevention of aminoglycoside-induced HC loss.<\/jats:p>","DOI":"10.1038\/srep41094","type":"journal-article","created":{"date-parts":[[2017,1,23]],"date-time":"2017-01-23T11:39:05Z","timestamp":1485171545000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["c-Myb knockdown increases the neomycin-induced damage to hair-cell-like HEI-OC1 cells in vitro"],"prefix":"10.1038","volume":"7","author":[{"given":"Xiaoyu","family":"Yu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaomin","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuping","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daogong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuechen","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaoying","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieyu","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shasha","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingliang","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfeng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renjie","family":"Chai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,1,23]]},"reference":[{"key":"BFsrep41094_CR1","doi-asserted-by":"publisher","first-page":"58","DOI":"10.3389\/fnagi.2015.00058","volume":"7","author":"AC Wong","year":"2015","unstructured":"Wong, A. C. & Ryan, A. F. Mechanisms of sensorineural cell damage, death and survival in the cochlea. Frontiers in aging neuroscience 7, 58, doi: 10.3389\/fnagi.2015.00058 (2015).","journal-title":"Frontiers in aging neuroscience"},{"key":"BFsrep41094_CR2","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1007\/s11684-016-0451-1","volume":"10","author":"W Li","year":"2016","unstructured":"Li, W., You, D., Chen, Y., Chai, R. & Li, H. Regeneration of hair cells in the mammalian vestibular system. Frontiers of medicine 10, 143\u2013151, doi: 10.1007\/s11684-016-0451-1 (2016).","journal-title":"Frontiers of medicine"},{"key":"BFsrep41094_CR3","doi-asserted-by":"crossref","unstructured":"Waqas, M. et al. Characterization of Lgr5+ progenitor cell transcriptomes in the apical and basal turns of the mouse cochlea. Oncotarget, doi: 10.18632\/oncotarget.8636 (2016).","DOI":"10.18632\/oncotarget.8636"},{"key":"BFsrep41094_CR4","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.tox.2008.04.015","volume":"249","author":"OW Guthrie","year":"2008","unstructured":"Guthrie, O. W. Aminoglycoside induced ototoxicity. Toxicology 249, 91\u201396, doi: 10.1016\/j.tox.2008.04.015 (2008).","journal-title":"Toxicology"},{"key":"BFsrep41094_CR5","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1016\/j.cell.2005.02.001","volume":"120","author":"RS Balaban","year":"2005","unstructured":"Balaban, R. S., Nemoto, S. & Finkel, T. Mitochondria, oxidants, and aging. Cell 120, 483\u2013495, doi: 10.1016\/j.cell.2005.02.001 (2005).","journal-title":"Cell"},{"key":"BFsrep41094_CR6","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/S0736-5748(99)00094-5","volume":"18","author":"T Huang","year":"2000","unstructured":"Huang, T. et al. Oxidative stress-induced apoptosis of cochlear sensory cells: otoprotective strategies. International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience 18, 259\u2013270 (2000).","journal-title":"International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience"},{"key":"BFsrep41094_CR7","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.heares.2011.05.008","volume":"281","author":"J Xie","year":"2011","unstructured":"Xie, J., Talaska, A. E. & Schacht, J. New developments in aminoglycoside therapy and ototoxicity. Hearing research 281, 28\u201337, doi: 10.1016\/j.heares.2011.05.008 (2011).","journal-title":"Hearing research"},{"key":"BFsrep41094_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/cne.20129","volume":"475","author":"DA Mangiardi","year":"2004","unstructured":"Mangiardi, D. A. et al. Progression of hair cell ejection and molecular markers of apoptosis in the avian cochlea following gentamicin treatment. The Journal of comparative neurology 475, 1\u201318, doi: 10.1002\/cne.20129 (2004).","journal-title":"The Journal of comparative neurology"},{"key":"BFsrep41094_CR9","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1007\/s10162-013-0404-1","volume":"14","author":"AB Coffin","year":"2013","unstructured":"Coffin, A. B., Rubel, E. W. & Raible, D. W. Bax, Bcl2, and p53 differentially regulate neomycin- and gentamicin-induced hair cell death in the zebrafish lateral line. Journal of the Association for Research in Otolaryngology: JARO 14, 645\u2013659, doi: 10.1007\/s10162-013-0404-1 (2013).","journal-title":"Journal of the Association for Research in Otolaryngology: JARO"},{"key":"BFsrep41094_CR10","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1126\/science.281.5381.1309","volume":"281","author":"DR Green","year":"1998","unstructured":"Green, D. R. & Reed, J. C. Mitochondria and apoptosis. Science 281, 1309\u20131312 (1998).","journal-title":"Science"},{"key":"BFsrep41094_CR11","doi-asserted-by":"publisher","first-page":"3017","DOI":"10.1038\/sj.onc.1202839","volume":"18","author":"IH Oh","year":"1999","unstructured":"Oh, I. H. & Reddy, E. P. The myb gene family in cell growth, differentiation and apoptosis. Oncogene 18, 3017\u20133033, doi: 10.1038\/sj.onc.1202839 (1999).","journal-title":"Oncogene"},{"key":"BFsrep41094_CR12","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1038\/nrc2439","volume":"8","author":"RG Ramsay","year":"2008","unstructured":"Ramsay, R. G. & Gonda, T. J. MYB function in normal and cancer cells. Nature reviews. Cancer 8, 523\u2013534, doi: 10.1038\/nrc2439 (2008).","journal-title":"Nature reviews. Cancer"},{"key":"BFsrep41094_CR13","doi-asserted-by":"publisher","first-page":"13762","DOI":"10.1073\/pnas.0700104104","volume":"104","author":"Y Drabsch","year":"2007","unstructured":"Drabsch, Y. et al. Mechanism of and requirement for estrogen-regulated MYB expression in estrogen-receptor-positive breast cancer cells. Proceedings of the National Academy of Sciences of the United States of America 104, 13762\u201313767, doi: 10.1073\/pnas.0700104104 (2007).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"BFsrep41094_CR14","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1161\/CIRCRESAHA.105.162628","volume":"102","author":"KM Kolodziejska","year":"2008","unstructured":"Kolodziejska, K. M. et al. c-Myb-dependent smooth muscle cell differentiation. Circulation research 102, 554\u2013561, doi: 10.1161\/CIRCRESAHA.105.162628 (2008).","journal-title":"Circulation research"},{"key":"BFsrep41094_CR15","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1634\/stemcells.2007-0293","volume":"26","author":"J Malaterre","year":"2008","unstructured":"Malaterre, J. et al. c-Myb is required for neural progenitor cell proliferation and maintenance of the neural stem cell niche in adult brain. Stem cells 26, 173\u2013181, doi: 10.1634\/stemcells.2007-0293 (2008).","journal-title":"Stem cells"},{"key":"BFsrep41094_CR16","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1016\/0092-8674(91)90099-K","volume":"65","author":"ML Mucenski","year":"1991","unstructured":"Mucenski, M. L. et al. A functional c-myb gene is required for normal murine fetal hepatic hematopoiesis. Cell 65, 677\u2013689 (1991).","journal-title":"Cell"},{"key":"BFsrep41094_CR17","doi-asserted-by":"publisher","first-page":"2194","DOI":"10.1073\/pnas.79.7.2194","volume":"79","author":"EH Westin","year":"1982","unstructured":"Westin, E. H. et al. Differential expression of the amv gene in human hematopoietic cells. Proceedings of the National Academy of Sciences of the United States of America 79, 2194\u20132198 (1982).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"BFsrep41094_CR18","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1038\/310249a0","volume":"310","author":"TJ Gonda","year":"1984","unstructured":"Gonda, T. J. & Metcalf, D. Expression of myb, myc and fos proto-oncogenes during the differentiation of a murine myeloid leukaemia. Nature 310, 249\u2013251 (1984).","journal-title":"Nature"},{"key":"BFsrep41094_CR19","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1007\/s11064-006-9278-5","volume":"32","author":"IK Hwang","year":"2007","unstructured":"Hwang, I. K. et al. c-Myb immunoreactivity, protein and mRNA levels significantly increase in the aged hippocampus proper in gerbils. Neurochemical research 32, 1091\u20131097, doi: 10.1007\/s11064-006-9278-5 (2007).","journal-title":"Neurochemical research"},{"key":"BFsrep41094_CR20","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.canlet.2013.09.022","volume":"343","author":"P Ye","year":"2014","unstructured":"Ye, P., Zhao, L., McGirr, C. & Gonda, T. J. MYB down-regulation enhances sensitivity of U937 myeloid leukemia cells to the histone deacetylase inhibitor LBH589 in vitro and in vivo . Cancer letters 343, 98\u2013106, doi: 10.1016\/j.canlet.2013.09.022 (2014).","journal-title":"Cancer letters"},{"key":"BFsrep41094_CR21","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.1093\/carcin\/bgs134","volume":"33","author":"SK Srivastava","year":"2012","unstructured":"Srivastava, S. K. et al. Myb overexpression overrides androgen depletion-induced cell cycle arrest and apoptosis in prostate cancer cells, and confers aggressive malignant traits: potential role in castration resistance. Carcinogenesis 33, 1149\u20131157, doi: 10.1093\/carcin\/bgs134 (2012).","journal-title":"Carcinogenesis"},{"key":"BFsrep41094_CR22","doi-asserted-by":"publisher","first-page":"5821","DOI":"10.1038\/sj.onc.1202971","volume":"18","author":"M Zorbas","year":"1999","unstructured":"Zorbas, M. et al. c-Myb is critical for murine colon development. Oncogene 18, 5821\u20135830, doi: 10.1038\/sj.onc.1202971 (1999).","journal-title":"Oncogene"},{"key":"BFsrep41094_CR23","doi-asserted-by":"publisher","first-page":"2720","DOI":"10.1101\/gad.10.21.2720","volume":"10","author":"J Frampton","year":"1996","unstructured":"Frampton, J., Ramqvist, T. & Graf, T. v-Myb of E26 leukemia virus up-regulates bcl-2 and suppresses apoptosis in myeloid cells. Genes & development 10, 2720\u20132731 (1996).","journal-title":"Genes & development"},{"key":"BFsrep41094_CR24","doi-asserted-by":"publisher","first-page":"1597","DOI":"10.1210\/en.2008-1079","volume":"150","author":"F Fang","year":"2009","unstructured":"Fang, F., Rycyzyn, M. A. & Clevenger, C. V. Role of c-Myb during prolactin-induced signal transducer and activator of transcription 5a signaling in breast cancer cells. Endocrinology 150, 1597\u20131606, doi: 10.1210\/en.2008-1079 (2009).","journal-title":"Endocrinology"},{"key":"BFsrep41094_CR25","first-page":"3410","volume":"20","author":"C Chen","year":"2016","unstructured":"Chen, C., Jia, K. Y., Zhang, H. L. & Fu, J. MiR-195 enhances cardiomyocyte apoptosis induced by hypoxia\/reoxygenation injury via downregulating c-myb. European review for medical and pharmacological sciences 20, 3410\u20133416 (2016).","journal-title":"European review for medical and pharmacological sciences"},{"key":"BFsrep41094_CR26","doi-asserted-by":"publisher","first-page":"9069","DOI":"10.18632\/oncotarget.6997","volume":"7","author":"P Mitra","year":"2016","unstructured":"Mitra, P., Yang, R. M., Sutton, J., Ramsay, R. G. & Gonda, T. J. CDK9 inhibitors selectively target estrogen receptor-positive breast cancer cells through combined inhibition of MYB and MCL-1 expression. Oncotarget 7, 9069\u20139083, doi: 10.18632\/oncotarget.6997 (2016).","journal-title":"Oncotarget"},{"key":"BFsrep41094_CR27","doi-asserted-by":"publisher","first-page":"3689","DOI":"10.1242\/dev.057836","volume":"138","author":"P Betancur","year":"2011","unstructured":"Betancur, P., Sauka-Spengler, T. & Bronner, M. A Sox10 enhancer element common to the otic placode and neural crest is activated by tissue-specific paralogs. Development 138, 3689\u20133698, doi: 10.1242\/dev.057836 (2011).","journal-title":"Development"},{"key":"BFsrep41094_CR28","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1159\/000071059","volume":"8","author":"GM Kalinec","year":"2003","unstructured":"Kalinec, G. M., Webster, P., Lim, D. J. & Kalinec, F. A cochlear cell line as an in vitro system for drug ototoxicity screening. Audiology & neuro-otology 8, 177\u2013189, doi: 71059 (2003).","journal-title":"Audiology & neuro-otology"},{"key":"BFsrep41094_CR29","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.heares.2005.04.003","volume":"207","author":"HJ Jeong","year":"2005","unstructured":"Jeong, H. J. et al. Hypoxia-induced IL-6 production is associated with activation of MAP kinase, HIF-1, and NF-kappaB on HEI-OC1 cells. Hearing Research 207, 59\u201367 (2005).","journal-title":"Hearing Research"},{"key":"BFsrep41094_CR30","doi-asserted-by":"publisher","first-page":"29621","DOI":"10.1038\/srep29621","volume":"6","author":"Z He","year":"2016","unstructured":"He, Z. et al. Reduced TRMU expression increases the sensitivity of hair-cell-like HEI-OC-1 cells to neomycin damage in vitro . Scientific reports 6, 29621, doi: 10.1038\/srep29621 (2016).","journal-title":"Scientific reports"},{"key":"BFsrep41094_CR31","doi-asserted-by":"crossref","unstructured":"Guan, M. et al. Inhibition of ARC decreases the survival of HEI-OC-1 cells after neomycin damage in vitro . Oncotarget, doi: 10.18632\/oncotarget.11336 (2016).","DOI":"10.18632\/oncotarget.11336"},{"key":"BFsrep41094_CR32","doi-asserted-by":"publisher","first-page":"248","DOI":"10.3389\/fncel.2014.00248","volume":"8","author":"S Sun","year":"2014","unstructured":"Sun, S. et al. In vivo overexpression of X-linked inhibitor of apoptosis protein protects against neomycin-induced hair cell loss in the apical turn of the cochlea during the ototoxic-sensitive period. Front Cell Neurosci 8, 248, doi: 10.3389\/fncel.2014.00248 (2014).","journal-title":"Front Cell Neurosci"},{"key":"BFsrep41094_CR33","doi-asserted-by":"publisher","first-page":"1218","DOI":"10.1523\/JNEUROSCI.22-04-01218.2002","volume":"22","author":"JI Matsui","year":"2002","unstructured":"Matsui, J. I., Ogilvie, J. M. & Warchol, M. E. Inhibition of caspases prevents ototoxic and ongoing hair cell death. The Journal of neuroscience: the official journal of the Society for Neuroscience 22, 1218\u20131227 (2002).","journal-title":"The Journal of neuroscience: the official journal of the Society for Neuroscience"},{"key":"BFsrep41094_CR34","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1007\/s12035-014-8841-3","volume":"52","author":"Y He","year":"2015","unstructured":"He, Y. et al. Inhibition of H3K4me2 Demethylation Protects Auditory Hair Cells from Neomycin-Induced Apoptosis. Molecular neurobiology 52, 196\u2013205, doi: 10.1007\/s12035-014-8841-3 (2015).","journal-title":"Molecular neurobiology"},{"key":"BFsrep41094_CR35","doi-asserted-by":"publisher","first-page":"e2136","DOI":"10.1038\/cddis.2016.35","volume":"7","author":"L Liu","year":"2016","unstructured":"Liu, L. et al. Wnt activation protects against neomycin-induced hair cell damage in the mouse cochlea. Cell Death Dis 7, e2136, doi: 10.1038\/cddis.2016.35 (2016).","journal-title":"Cell Death Dis"},{"key":"BFsrep41094_CR36","doi-asserted-by":"publisher","first-page":"e1605","DOI":"10.1038\/cddis.2014.549","volume":"6","author":"Y Chen","year":"2015","unstructured":"Chen, Y. et al. Bmi1 regulates auditory hair cell survival by maintaining redox balance. Cell death & disease 6, e1605, doi: 10.1038\/cddis.2014.549 (2015).","journal-title":"Cell death & disease"},{"key":"BFsrep41094_CR37","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1016\/j.neuroscience.2009.02.085","volume":"161","author":"YH Choung","year":"2009","unstructured":"Choung, Y. H. et al. Generation of highly-reactive oxygen species is closely related to hair cell damage in rat organ of Corti treated with gentamicin. Neuroscience 161, 214\u2013226, doi: 10.1016\/j.neuroscience.2009.02.085 (2009).","journal-title":"Neuroscience"},{"key":"BFsrep41094_CR38","doi-asserted-by":"publisher","first-page":"e82684","DOI":"10.1371\/journal.pone.0082684","volume":"8","author":"LH Kasper","year":"2013","unstructured":"Kasper, L. H. et al. Genetic interaction between mutations in c-Myb and the KIX domains of CBP and p300 affects multiple blood cell lineages and influences both gene activation and repression. PloS one 8, e82684, doi: 10.1371\/journal.pone.0082684 (2013).","journal-title":"PloS one"},{"key":"BFsrep41094_CR39","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.ijantimicag.2008.09.001","volume":"33","author":"E Durante-Mangoni","year":"2009","unstructured":"Durante-Mangoni, E., Grammatikos, A., Utili, R. & Falagas, M. E. Do we still need the aminoglycosides? International journal of antimicrobial agents 33, 201\u2013205, doi: 10.1016\/j.ijantimicag.2008.09.001 (2009).","journal-title":"International journal of antimicrobial agents"},{"key":"BFsrep41094_CR40","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1038\/jp.2012.105","volume":"33","author":"E Zimmerman","year":"2013","unstructured":"Zimmerman, E. & Lahav, A. Ototoxicity in preterm infants: effects of genetics, aminoglycosides, and loud environmental noise. Journal of perinatology: official journal of the California Perinatal Association 33, 3\u20138, doi: 10.1038\/jp.2012.105 (2013).","journal-title":"Journal of perinatology: official journal of the California Perinatal Association"},{"key":"BFsrep41094_CR41","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1146\/annurev.biochem.68.1.383","volume":"68","author":"WC Earnshaw","year":"1999","unstructured":"Earnshaw, W. C., Martins, L. M. & Kaufmann, S. H. Mammalian caspases: structure, activation, substrates, and functions during apoptosis. Annual review of biochemistry 68, 383\u2013424, doi: 10.1146\/annurev.biochem.68.1.383 (1999).","journal-title":"Annual review of biochemistry"},{"key":"BFsrep41094_CR42","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/S0092-8674(00)80564-4","volume":"96","author":"DL Vaux","year":"1999","unstructured":"Vaux, D. L. & Korsmeyer, S. J. Cell death in development. Cell 96, 245\u2013254 (1999).","journal-title":"Cell"},{"key":"BFsrep41094_CR43","doi-asserted-by":"publisher","first-page":"11549","DOI":"10.1074\/jbc.274.17.11549","volume":"274","author":"H Zou","year":"1999","unstructured":"Zou, H., Li, Y., Liu, X. & Wang, X. An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9. The Journal of biological chemistry 274, 11549\u201311556 (1999).","journal-title":"The Journal of biological chemistry"},{"key":"BFsrep41094_CR44","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1016\/S0968-0004(01)01844-8","volume":"26","author":"C Adrain","year":"2001","unstructured":"Adrain, C. & Martin, S. J. The mitochondrial apoptosome: a killer unleashed by the cytochrome seas. Trends in biochemical sciences 26, 390\u2013397 (2001).","journal-title":"Trends in biochemical sciences"},{"key":"BFsrep41094_CR45","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/S0070-2153(06)77005-3","volume":"77","author":"R McFarland","year":"2007","unstructured":"McFarland, R., Taylor, R. W. & Turnbull, D. M. Mitochondrial disease\u2013its impact, etiology, and pathology. Current topics in developmental biology 77, 113\u2013155, doi: 10.1016\/S0070-2153(06)77005-3 (2007).","journal-title":"Current topics in developmental biology"},{"key":"BFsrep41094_CR46","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1113\/jphysiol.2005.085951","volume":"567","author":"W Marcotti","year":"2005","unstructured":"Marcotti, W., van Netten, S. M. & Kros, C. J. The aminoglycoside antibiotic dihydrostreptomycin rapidly enters mouse outer hair cells through the mechano-electrical transducer channels. The Journal of physiology 567, 505\u2013521, doi: 10.1113\/jphysiol.2005.085951 (2005).","journal-title":"The Journal of physiology"},{"key":"BFsrep41094_CR47","doi-asserted-by":"publisher","first-page":"F21","DOI":"10.1084\/jem.192.8.F21","volume":"192","author":"S Roy","year":"2000","unstructured":"Roy, S. & Nicholson, D. W. Cross-talk in cell death signaling. The Journal of experimental medicine 192, F21\u201325 (2000).","journal-title":"The Journal of experimental medicine"},{"key":"BFsrep41094_CR48","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1093\/emboj\/20.5.998","volume":"20","author":"SB Bratton","year":"2001","unstructured":"Bratton, S. B. et al. Recruitment, activation and retention of caspases-9 and -3 by Apaf-1 apoptosome and associated XIAP complexes. The EMBO journal 20, 998\u20131009, doi: 10.1093\/emboj\/20.5.998 (2001).","journal-title":"The EMBO journal"},{"key":"BFsrep41094_CR49","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1182\/blood-2014-05-576470","volume":"125","author":"D Jing","year":"2015","unstructured":"Jing, D. et al. Opposing regulation of BIM and BCL2 controls glucocorticoid-induced apoptosis of pediatric acute lymphoblastic leukemia cells. Blood 125, 273\u2013283, doi: 10.1182\/blood-2014-05-576470 (2015).","journal-title":"Blood"},{"key":"BFsrep41094_CR50","doi-asserted-by":"publisher","first-page":"3296","DOI":"10.1073\/pnas.94.7.3296","volume":"94","author":"P Salomoni","year":"1997","unstructured":"Salomoni, P., Perrotti, D., Martinez, R., Franceschi, C. & Calabretta, B. Resistance to apoptosis in CTLL-2 cells constitutively expressing c-Myb is associated with induction of BCL-2 expression and Myb-dependent regulation of bcl-2 promoter activity. Proceedings of the National Academy of Sciences of the United States of America 94, 3296\u20133301 (1997).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"BFsrep41094_CR51","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1111\/j.1365-2567.2004.02073.x","volume":"114","author":"G Lang","year":"2005","unstructured":"Lang, G., Gombert, W. M. & Gould, H. J. A transcriptional regulatory element in the coding sequence of the human Bcl-2 gene. Immunology 114, 25\u201336, doi: 10.1111\/j.1365-2567.2004.02073.x (2005).","journal-title":"Immunology"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep41094.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep41094","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep41094.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T21:34:31Z","timestamp":1671831271000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep41094"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,1,23]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,3,13]]}},"alternative-id":["BFsrep41094"],"URL":"https:\/\/doi.org\/10.1038\/srep41094","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,1,23]]},"assertion":[{"value":"27 September 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 December 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 January 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"41094"}}