{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T23:41:25Z","timestamp":1794440485328,"version":"4.9.1"},"reference-count":62,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2022,4,4]],"date-time":"2022-04-04T00:00:00Z","timestamp":1649030400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,4,4]],"date-time":"2022-04-04T00:00:00Z","timestamp":1649030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["30730027"],"award-info":[{"award-number":["30730027"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["30871240"],"award-info":[{"award-number":["30871240"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Death Dis"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The anti-apoptotic protein HAX-1 has been proposed to modulate mitochondrial membrane potential, calcium signaling and actin remodeling.<jats:italic>HAX-1<\/jats:italic>mutation or deficiency results in severe congenital neutropenia (SCN), loss of lymphocytes and neurological impairments by largely unknown mechanisms. Here, we demonstrate that the activation of c-Abl kinase in response to oxidative or genotoxic stress is dependent on HAX-1 association. Cellular reactive oxygen species (ROS) accumulation is inhibited by HAX-1-dependent c-Abl activation, which greatly contributes to the antiapoptotic role of HAX-1 in stress. HAX-1 (Q190X), a loss-of-function mutant responsible for SCN, fails to bind with and activate c-Abl, leading to dysregulated cellular ROS levels, damaged mitochondrial membrane potential and eventually apoptosis. The extensive apoptosis of lymphocytes and neurons in<jats:italic>Hax-1<\/jats:italic>-deficient mice could also be remarkably suppressed by c-Abl activation. These findings underline the important roles of ROS clearance in HAX-1-mediated anti-apoptosis by c-Abl kinase activation, providing new insight into the pathology and treatment of HAX-1-related hereditary disease or tumorigenesis.<\/jats:p>","DOI":"10.1038\/s41419-022-04748-2","type":"journal-article","created":{"date-parts":[[2022,4,4]],"date-time":"2022-04-04T08:06:53Z","timestamp":1649059613000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Anti-apoptotic HAX-1 suppresses cell apoptosis by promoting c-Abl kinase-involved ROS clearance"],"prefix":"10.1038","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2173-855X","authenticated-orcid":false,"given":"Qincai","family":"Dong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dapei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huailong","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5772-9482","authenticated-orcid":false,"given":"Lin","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang-Fei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hainan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiayang","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caiwei","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanwen","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7981-6114","authenticated-orcid":false,"given":"Cheng","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6369-9259","authenticated-orcid":false,"given":"Xuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,4,4]]},"reference":[{"key":"4748_CR1","doi-asserted-by":"crossref","first-page":"2736","DOI":"10.4049\/jimmunol.158.6.2736","volume":"158","author":"Y Suzuki","year":"1997","unstructured":"Suzuki Y, Demoliere C, Kitamura D, Takeshita H, Deuschle U, Watanabe T. HAX-1, a novel intracellular protein, localized on mitochondria, directly associates with HS1, a substrate of Src family tyrosine kinases. J Immunol. 1997;158:2736\u201344.","journal-title":"J Immunol"},{"key":"4748_CR2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-10-76","volume":"10","author":"A Trebinska","year":"2010","unstructured":"Trebinska A, Rembiszewska A, Ciosek K, Ptaszynski K, Rowinski S, Kupryjanczyk J, et al. HAX-1 overexpression, splicing and cellular localization in tumors. BMC Cancer. 2010;10:76.","journal-title":"BMC Cancer"},{"key":"4748_CR3","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1080\/15384047.2019.1617562","volume":"20","author":"Z Wu","year":"2019","unstructured":"Wu Z, Ai X, Hu H, Wang S, Wang Y, Kang F, et al. Hematopoietic-substrate-1 associated protein X-1 (HAX-1) regulates liver cancer cells growth, metastasis, and angiogenesis through Akt. Cancer Biol Ther. 2019;20:1223\u201333.","journal-title":"Cancer Biol Ther"},{"key":"4748_CR4","doi-asserted-by":"publisher","first-page":"1266","DOI":"10.1016\/j.yjmcc.2009.10.028","volume":"48","author":"SV Yap","year":"2010","unstructured":"Yap SV, Vafiadaki E, Strong J, Kontrogianni-Konstantopoulos A. HAX-1: a multifaceted antiapoptotic protein localizing in the mitochondria and the sarcoplasmic reticulum of striated muscle cells. J Mol Cell Cardiol. 2010;48:1266\u201379.","journal-title":"J Mol Cell Cardiol"},{"key":"4748_CR5","doi-asserted-by":"publisher","first-page":"420","DOI":"10.3389\/fncel.2017.00420","volume":"11","author":"X Deng","year":"2017","unstructured":"Deng X, Song L, Zhao W, Wei Y, Guo XB. HAX-1 protects glioblastoma cells from apoptosis through the Akt1 pathway. Front Cell Neurosci. 2017;11:420.","journal-title":"Front Cell Neurosci"},{"key":"4748_CR6","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1002\/stem.2741","volume":"36","author":"XB Guo","year":"2018","unstructured":"Guo XB, Deng X, Wei Y. Hematopoietic substrate-1-associated protein X-1 regulates the proliferation and apoptosis of endothelial progenitor cells through akt pathway modulation. Stem Cells. 2018;36:406\u201319.","journal-title":"Stem Cells"},{"key":"4748_CR7","first-page":"218","volume":"53","author":"M Szwarc","year":"2007","unstructured":"Szwarc M, Sarnowska E, Grzybowska EA. [HAX-1 protein: multifunctional factor involved in apoptosis, cell migration, endocytosis and mRNA transport]. Postepy Biochem. 2007;53:218\u201327.","journal-title":"Postepy Biochem"},{"key":"4748_CR8","doi-asserted-by":"publisher","first-page":"2776","DOI":"10.3892\/or.2015.4202","volume":"34","author":"J Yan","year":"2015","unstructured":"Yan J, Ma C, Cheng J, Li Z, Liu C. HAX-1 inhibits apoptosis in prostate cancer through the suppression of caspase-9 activation. Oncol Rep. 2015;34:2776\u201381.","journal-title":"Oncol Rep"},{"key":"4748_CR9","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1038\/nature06604","volume":"452","author":"JR Chao","year":"2008","unstructured":"Chao JR, Parganas E, Boyd K, Hong CY, Opferman JT, Ihle JN. Hax1-mediated processing of HtrA2 by Parl allows survival of lymphocytes and neurons. Nature. 2008;452:98\u2013102.","journal-title":"Nature"},{"key":"4748_CR10","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1161\/01.RES.0000237387.05259.a5","volume":"99","author":"Y Han","year":"2006","unstructured":"Han Y, Chen YS, Liu Z, Bodyak N, Rigor D, Bisping E, et al. Overexpression of HAX-1 protects cardiac myocytes from apoptosis through caspase-9 inhibition. Circ Res. 2006;99:415\u201323.","journal-title":"Circ Res"},{"key":"4748_CR11","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1016\/j.cellbi.2009.02.005","volume":"33","author":"WB Li","year":"2009","unstructured":"Li WB, Feng J, Geng SM, Zhang PY, Yan XN, Hu G, et al. Induction of apoptosis by Hax-1 siRNA in melanoma cells. Cell Biol Int. 2009;33:548\u201354.","journal-title":"Cell Biol Int"},{"key":"4748_CR12","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1007\/s11064-011-0641-9","volume":"37","author":"A Rami","year":"2012","unstructured":"Rami A, Langhagen A. Specific alterations of the HtrA2\/HAX-1 ratio in the penumbra upon focal cerebral ischemia in mice. Neurochem Res. 2012;37:548\u201356.","journal-title":"Neurochem Res"},{"key":"4748_CR13","first-page":"3586132","volume":"2018","author":"X Li","year":"2018","unstructured":"Li X, Qu B. Critical role of HAX-1 in promoting avian influenza virus replication in lung epithelial. Cells 2018;2018:3586132.","journal-title":"Cells"},{"key":"4748_CR14","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1038\/ng1940","volume":"39","author":"C Klein","year":"2007","unstructured":"Klein C, Grudzien M, Appaswamy G, Germeshausen M, Sandrock I, Schaffer AA, et al. HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease). Nat Genet. 2007;39:86\u201392.","journal-title":"Nat Genet"},{"key":"4748_CR15","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1083\/jcb.201010143","volume":"193","author":"PJ Cavnar","year":"2011","unstructured":"Cavnar PJ, Berthier E, Beebe DJ, Huttenlocher A. Hax1 regulates neutrophil adhesion and motility through RhoA. J Cell Biol. 2011;193:465\u201373.","journal-title":"J Cell Biol"},{"key":"4748_CR16","doi-asserted-by":"publisher","first-page":"3157","DOI":"10.1002\/ajmg.a.33748","volume":"152A","author":"K Boztug","year":"2010","unstructured":"Boztug K, Ding XQ, Hartmann H, Ziesenitz L, Schaffer AA, Diestelhorst J, et al. HAX1 mutations causing severe congenital neuropenia and neurological disease lead to cerebral microstructural abnormalities documented by quantitative MRI. Am J Med Genet A. 2010;152A:3157\u201363.","journal-title":"Am J Med Genet A"},{"key":"4748_CR17","doi-asserted-by":"publisher","first-page":"116928","DOI":"10.1016\/j.jns.2020.116928","volume":"415","author":"Y Kawamoto","year":"2020","unstructured":"Kawamoto Y, Ayaki T, Urushitani M, Ito H, Takahashi R. Accumulation of HAX-1 and PARL in brainstem- and cortical-type Lewy bodies in Parkinson\u2019s disease and dementia with Lewy bodies. J Neurol Sci. 2020;415:116928.","journal-title":"J Neurol Sci"},{"key":"4748_CR18","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/S0065-230X(02)85003-5","volume":"85","author":"AM Pendergast","year":"2002","unstructured":"Pendergast AM. The Abl family kinases: mechanisms of regulation and signaling. Adv Cancer Res. 2002;85:51\u2013100.","journal-title":"Adv Cancer Res"},{"key":"4748_CR19","doi-asserted-by":"publisher","first-page":"612","DOI":"10.3892\/mmr.2020.11156","volume":"22","author":"AA Bohio","year":"2020","unstructured":"Bohio AA, Wang R, Zeng X, Ba X. c\u2011Abl\u2011mediated tyrosine phosphorylation of DNA damage response proteins and implications in important cellular functions (Review). Mol Med Rep. 2020;22:612\u20139.","journal-title":"Mol Med Rep"},{"key":"4748_CR20","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1242\/jcs.175521","volume":"129","author":"A Khatri","year":"2016","unstructured":"Khatri A, Wang J, Pendergast AM. Multifunctional Abl kinases in health and disease. J Cell Sci. 2016;129:9\u201316.","journal-title":"J Cell Sci"},{"key":"4748_CR21","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1038\/21690","volume":"399","author":"JG Gong","year":"1999","unstructured":"Gong JG, Costanzo A, Yang HQ, Melino G, Kaelin WG Jr., Levrero M, et al. The tyrosine kinase c-Abl regulates p73 in apoptotic response to cisplatin-induced DNA damage. Nature. 1999;399:806\u20139.","journal-title":"Nature"},{"key":"4748_CR22","first-page":"791","volume":"11","author":"A Goga","year":"1995","unstructured":"Goga A, Liu X, Hambuch TM, Senechal K, Major E, Berk AJ, et al. p53 dependent growth suppression by the c-Abl nuclear tyrosine kinase. Oncogene. 1995;11:791\u20139.","journal-title":"Oncogene"},{"key":"4748_CR23","doi-asserted-by":"publisher","first-page":"26457","DOI":"10.1074\/jbc.271.43.26457","volume":"271","author":"ZM Yuan","year":"1996","unstructured":"Yuan ZM, Huang Y, Fan MM, Sawyers C, Kharbanda S, Kufe D. Genotoxic drugs induce interaction of the c-Abl tyrosine kinase and the tumor suppressor protein p53. J Biol Chem. 1996;271:26457\u201360.","journal-title":"J Biol Chem"},{"key":"4748_CR24","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1038\/21704","volume":"399","author":"ZM Yuan","year":"1999","unstructured":"Yuan ZM, Shioya H, Ishiko T, Sun X, Gu J, Huang YY, et al. p73 is regulated by tyrosine kinase c-Abl in the apoptotic response to DNA damage. Nature. 1999;399:814\u20137.","journal-title":"Nature"},{"key":"4748_CR25","doi-asserted-by":"publisher","first-page":"5643","DOI":"10.1038\/sj.onc.1203878","volume":"19","author":"JY Wang","year":"2000","unstructured":"Wang JY. Regulation of cell death by the Abl tyrosine kinase. Oncogene. 2000;19:5643\u201350.","journal-title":"Oncogene"},{"key":"4748_CR26","doi-asserted-by":"publisher","first-page":"13131","DOI":"10.1073\/pnas.93.23.13131","volume":"93","author":"M Dorsch","year":"1996","unstructured":"Dorsch M, Goff SP. Increased sensitivity to apoptotic stimuli in c-abl-deficient progenitor B-cell lines. Proc Natl Acad Sci USA. 1996;93:13131\u20136.","journal-title":"Proc Natl Acad Sci USA"},{"key":"4748_CR27","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.1016\/S0896-6273(00)80646-7","volume":"21","author":"AJ Koleske","year":"1998","unstructured":"Koleske AJ, Gifford AM, Scott ML, Nee M, Bronson RT, Miczek KA, et al. Essential roles for the Abl and Arg tyrosine kinases in neurulation. Neuron. 1998;21:1259\u201372.","journal-title":"Neuron"},{"key":"4748_CR28","doi-asserted-by":"publisher","first-page":"29667","DOI":"10.1074\/jbc.M301292200","volume":"278","author":"C Cao","year":"2003","unstructured":"Cao C, Leng Y, Kufe D. Catalase activity is regulated by c-Abl and Arg in the oxidative stress response. J Biol Chem. 2003;278:29667\u201375.","journal-title":"J Biol Chem"},{"key":"4748_CR29","doi-asserted-by":"publisher","first-page":"11465","DOI":"10.1074\/jbc.C100050200","volume":"276","author":"C Cao","year":"2001","unstructured":"Cao C, Ren X, Kharbanda S, Koleske AJ, Prasad KV, Kufe D. The ARG tyrosine kinase interacts with Siva-1 in the apoptotic response to oxidative stress. J Biol Chem. 2001;276:11465\u20138.","journal-title":"J Biol Chem"},{"key":"4748_CR30","doi-asserted-by":"publisher","first-page":"683097","DOI":"10.1155\/2012\/683097","volume":"2012","author":"S Gonfloni","year":"2012","unstructured":"Gonfloni S, Maiani E, Di Bartolomeo C, Diederich M, Cesareni G. Oxidative stress, DNA damage, and c-Abl signaling: At the crossroad in neurodegenerative diseases? Int J Cell Biol. 2012;2012:683097.","journal-title":"Int J Cell Biol"},{"key":"4748_CR31","doi-asserted-by":"publisher","first-page":"7470","DOI":"10.1074\/jbc.275.11.7470","volume":"275","author":"X Sun","year":"2000","unstructured":"Sun X, Wu F, Datta R, Kharbanda S, Kufe D. Interaction between protein kinase C delta and the c-Abl tyrosine kinase in the cellular response to oxidative stress. J Biol Chem. 2000;275:7470\u20133.","journal-title":"J Biol Chem"},{"key":"4748_CR32","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1126\/science.1192912","volume":"330","author":"Z Guo","year":"2010","unstructured":"Guo Z, Kozlov S, Lavin MF, Person MD, Paull TT. ATM activation by oxidative stress. Science. 2010;330:517\u201321.","journal-title":"Science"},{"key":"4748_CR33","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1038\/cdd.2010.132","volume":"18","author":"V Meltser","year":"2011","unstructured":"Meltser V, Ben-Yehoyada M, Shaul Y. c-Abl tyrosine kinase in the DNA damage response: cell death and more. Cell Death Differ. 2011;18:2\u20134.","journal-title":"Cell Death Differ"},{"key":"4748_CR34","doi-asserted-by":"publisher","first-page":"1824","DOI":"10.1101\/gad.1223504","volume":"18","author":"B Li","year":"2004","unstructured":"Li B, Wang X, Rasheed N, Hu Y, Boast S, Ishii T, et al. Distinct roles of c-Abl and Atm in oxidative stress response are mediated by protein kinase C delta. Genes Dev. 2004;18:1824\u201337.","journal-title":"Genes Dev"},{"key":"4748_CR35","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1038\/376785a0","volume":"376","author":"S Kharbanda","year":"1995","unstructured":"Kharbanda S, Ren R, Pandey P, Shafman TD, Feller SM, Weichselbaum RR, et al. Activation of the c-Abl tyrosine kinase in the stress response to DNA-damaging agents. Nature. 1995;376:785\u20138.","journal-title":"Nature"},{"key":"4748_CR36","doi-asserted-by":"publisher","first-page":"17237","DOI":"10.1074\/jbc.C000099200","volume":"275","author":"X Sun","year":"2000","unstructured":"Sun X, Majumder P, Shioya H, Wu F, Kumar S, Weichselbaum R, et al. Activation of the cytoplasmic c-Abl tyrosine kinase by reactive oxygen species. J Biol Chem. 2000;275:17237\u201340.","journal-title":"J Biol Chem"},{"key":"4748_CR37","doi-asserted-by":"publisher","first-page":"1779","DOI":"10.1038\/sj.onc.1201708","volume":"16","author":"R Agami","year":"1998","unstructured":"Agami R, Shaul Y. The kinase activity of c-Abl but not v-Abl is potentiated by direct interaction with RFXI, a protein that binds the enhancers of several viruses and cell-cycle regulated genes. Oncogene. 1998;16:1779\u201388.","journal-title":"Oncogene"},{"key":"4748_CR38","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1016\/0968-0004(94)90129-5","volume":"19","author":"SM Feller","year":"1994","unstructured":"Feller SM, Ren R, Hanafusa H, Baltimore D. SH2 and SH3 domains as molecular adhesives: the interactions of Crk and Abl. Trends Biochem Sci. 1994;19:453\u20138.","journal-title":"Trends Biochem Sci"},{"key":"4748_CR39","doi-asserted-by":"publisher","first-page":"3884","DOI":"10.1128\/MCB.23.11.3884-3896.2003","volume":"23","author":"KQ Tanis","year":"2003","unstructured":"Tanis KQ, Veach D, Duewel HS, Bornmann WG, Koleske AJ. Two distinct phosphorylation pathways have additive effects on Abl family kinase activation. Mol Cell Biol. 2003;23:3884\u201396.","journal-title":"Mol Cell Biol"},{"key":"4748_CR40","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1042\/bj20021539","volume":"370","author":"P Soubeyran","year":"2003","unstructured":"Soubeyran P, Barac A, Szymkiewicz I, Dikic I. Cbl-ArgBP2 complex mediates ubiquitination and degradation of c-Abl. Biochem J. 2003;370:29\u201334.","journal-title":"Biochem J"},{"key":"4748_CR41","doi-asserted-by":"publisher","first-page":"1759","DOI":"10.1016\/S0960-9822(01)00538-3","volume":"11","author":"A Echarri","year":"2001","unstructured":"Echarri A, Pendergast AM. Activated c-Abl is degraded by the ubiquitin-dependent proteasome pathway. Curr Biol. 2001;11:1759\u201365.","journal-title":"Curr Biol"},{"key":"4748_CR42","doi-asserted-by":"publisher","first-page":"21683","DOI":"10.1073\/pnas.1016311108","volume":"107","author":"JH Mao","year":"2010","unstructured":"Mao JH, Sun XY, Liu JX, Zhang QY, Liu P, Huang QH, et al. As4S4 targets RING-type E3 ligase c-CBL to induce degradation of BCR-ABL in chronic myelogenous leukemia. Proc Natl Acad Sci USA. 2010;107:21683\u20138.","journal-title":"Proc Natl Acad Sci USA"},{"key":"4748_CR43","doi-asserted-by":"publisher","first-page":"39609","DOI":"10.1074\/jbc.M305770200","volume":"278","author":"C Cao","year":"2003","unstructured":"Cao C, Leng Y, Huang W, Liu X, Kufe D. Glutathione peroxidase 1 is regulated by the c-Abl and Arg tyrosine kinases. J Biol Chem. 2003;278:39609\u201314.","journal-title":"J Biol Chem"},{"key":"4748_CR44","doi-asserted-by":"crossref","unstructured":"Chen J, Yang S, Wu C, Cui Z, Wan Y, Xu G, et al. Novel role of HAX-1 in neurons protection after spinal cord injury involvement of IRE-1. 2020;45:2302\u201311.","DOI":"10.1007\/s11064-020-03088-x"},{"key":"4748_CR45","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1517\/14728222.2011.561787","volume":"15","author":"T Simmen","year":"2011","unstructured":"Simmen T. Hax-1: a regulator of calcium signaling and apoptosis progression with multiple roles in human disease. Expert Opin Ther Targets. 2011;15:741\u201351.","journal-title":"Expert Opin Ther Targets"},{"key":"4748_CR46","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1091\/mbc.e08-06-0587","volume":"20","author":"E Vafiadaki","year":"2009","unstructured":"Vafiadaki E, Arvanitis DA, Pagakis SN, Papalouka V, Sanoudou D, Kontrogianni-Konstantopoulos A, et al. The anti-apoptotic protein HAX-1 interacts with SERCA2 and regulates its protein levels to promote cell survival. Mol Biol Cell. 2009;20:306\u201318.","journal-title":"Mol Biol Cell"},{"key":"4748_CR47","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1161\/01.RES.0000239408.03169.94","volume":"99","author":"J Shaw","year":"2006","unstructured":"Shaw J, Kirshenbaum LA. HAX-1 represses postmitochondrial caspase-9 activation and cell death during hypoxia-reoxygenation. Circ Res. 2006;99:336\u20138.","journal-title":"Circ Res"},{"key":"4748_CR48","doi-asserted-by":"publisher","first-page":"1622","DOI":"10.1038\/cdd.2009.110","volume":"16","author":"DV Jeyaraju","year":"2009","unstructured":"Jeyaraju DV, Cisbani G, De Brito OM, Koonin EV, Pellegrini L. Hax1 lacks BH modules and is peripherally associated to heavy membranes: implications for Omi\/HtrA2 and PARL activity in the regulation of mitochondrial stress and apoptosis. Cell Death Differ. 2009;16:1622\u20139.","journal-title":"Cell Death Differ"},{"key":"4748_CR49","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1016\/S0092-8674(03)00194-6","volume":"112","author":"B Nagar","year":"2003","unstructured":"Nagar B, Hantschel O, Young MA, Scheffzek K, Veach D, Bornmann W, et al. Structural basis for the autoinhibition of c-Abl tyrosine kinase. Cell. 2003;112:859\u201371.","journal-title":"Cell"},{"key":"4748_CR50","doi-asserted-by":"publisher","first-page":"2456","DOI":"10.1101\/gad.11.19.2456","volume":"11","author":"ST Wen","year":"1997","unstructured":"Wen ST, Van Etten RA. The PAG gene product, a stress-induced protein with antioxidant properties, is an Abl SH3-binding protein and a physiological inhibitor of c-Abl tyrosine kinase activity. Genes Dev. 1997;11:2456\u201367.","journal-title":"Genes Dev"},{"key":"4748_CR51","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1038\/sj.cdd.4400626","volume":"7","author":"Y Shaul","year":"2000","unstructured":"Shaul Y. c-Abl: activation and nuclear targets. Cell Death Differ. 2000;7:10\u20136.","journal-title":"Cell Death Differ"},{"key":"4748_CR52","first-page":"873","volume":"63","author":"PD Fan","year":"2003","unstructured":"Fan PD, Cong F, Goff SP. Homo- and hetero-oligomerization of the c-Abl kinase and Abelson-interactor-1. Cancer Res. 2003;63:873\u20137.","journal-title":"Cancer Res"},{"key":"4748_CR53","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1038\/nrc3563","volume":"13","author":"EK Greuber","year":"2013","unstructured":"Greuber EK, Smith-Pearson P, Wang J, Pendergast AM. Role of ABL family kinases in cancer: from leukaemia to solid tumours. Nat Rev Cancer. 2013;13:559\u201371.","journal-title":"Nat Rev Cancer"},{"key":"4748_CR54","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.jmb.2006.10.057","volume":"367","author":"E Vafiadaki","year":"2007","unstructured":"Vafiadaki E, Sanoudou D, Arvanitis DA, Catino DH, Kranias EG, Kontrogianni-Konstantopoulos A. Phospholamban interacts with HAX-1, a mitochondrial protein with anti-apoptotic function. J Mol Biol. 2007;367:65\u201379.","journal-title":"J Mol Biol"},{"key":"4748_CR55","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.3892\/ol.2012.634","volume":"3","author":"LJ Yang","year":"2012","unstructured":"Yang LJ, Chen Y, He J, Yi S, Wen L, Zhao S, et al. Effects of gambogic acid on the activation of caspase-3 and downregulation of SIRT1 in RPMI-8226 multiple myeloma cells via the accumulation of ROS. Oncol Lett. 2012;3:1159\u201365.","journal-title":"Oncol Lett"},{"key":"4748_CR56","doi-asserted-by":"publisher","first-page":"6737","DOI":"10.1007\/s11033-012-1498-y","volume":"39","author":"JS Lee","year":"2012","unstructured":"Lee JS, Yang EJ, Kim IS. Hydroquinone-induced apoptosis of human lymphocytes through caspase 9\/3 pathway. Mol Biol Rep. 2012;39:6737\u201343.","journal-title":"Mol Biol Rep"},{"key":"4748_CR57","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1007\/s00431-010-1150-6","volume":"169","author":"M Faiyaz-Ul-Haque","year":"2010","unstructured":"Faiyaz-Ul-Haque M, Al-Jefri A, Al-Dayel F, Bhuiyan JA, Abalkhail HA, Al-Nounou R, et al. A novel HAX1 gene mutation in severe congenital neutropenia (SCN) associated with neurological manifestations. Eur J Pediatr. 2010;169:661\u20136.","journal-title":"Eur J Pediatr"},{"key":"4748_CR58","first-page":"349","volume":"28","author":"X Luo","year":"2011","unstructured":"Luo X, Li Z, Li X, Wang G, Liu W, Dong S, et al. hSav1 interacts with HAX1 and attenuates its anti-apoptotic effects in MCF-7 breast cancer cells. Int J Mol Med. 2011;28:349\u201355.","journal-title":"Int J Mol Med"},{"key":"4748_CR59","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.febslet.2009.11.009","volume":"584","author":"A Baruzzi","year":"2010","unstructured":"Baruzzi A, Iacobucci I, Soverini S, Lowell CA, Martinelli G, Berton G. c-Abl and Src-family kinases cross-talk in regulation of myeloid cell migration. FEBS Lett. 2010;584:15\u201321.","journal-title":"FEBS Lett"},{"key":"4748_CR60","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1016\/j.bcmd.2010.12.010","volume":"46","author":"CJ Ball","year":"2011","unstructured":"Ball CJ, King MR. Role of c-Abl in L-selectin shedding from the neutrophil surface. Blood Cells Mol Dis. 2011;46:246\u201351.","journal-title":"Blood Cells Mol Dis"},{"key":"4748_CR61","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-10-438","volume":"10","author":"JE Hwang","year":"2010","unstructured":"Hwang JE, Yoon JY, Bae WK, Shim HJ, Cho SH, Chung IJ. Imatinib induced severe skin reactions and neutropenia in a patient with gastrointestinal stromal tumor. BMC Cancer. 2010;10:438.","journal-title":"BMC Cancer"},{"key":"4748_CR62","doi-asserted-by":"publisher","first-page":"318","DOI":"10.3324\/haematol.2011.055038","volume":"97","author":"SL Xue","year":"2012","unstructured":"Xue SL, Li JL, Zou JY, Su J, Chen SN, Wu DP. A novel compound heterozygous HAX1 mutation in a Chinese patient with severe congenital neutropenia and chronic myelomonocytic leukemia transformation but without neurodevelopmental abnormalities. Haematologica. 2012;97:318\u201320.","journal-title":"Haematologica"}],"container-title":["Cell Death &amp; Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41419-022-04748-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41419-022-04748-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41419-022-04748-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T14:25:51Z","timestamp":1675175151000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41419-022-04748-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,4]]},"references-count":62,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["4748"],"URL":"https:\/\/doi.org\/10.1038\/s41419-022-04748-2","relation":{},"ISSN":["2041-4889"],"issn-type":[{"value":"2041-4889","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,4]]},"assertion":[{"value":"7 July 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 March 2022","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 March 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 April 2022","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The animal studies were approved by the Institutional Ethics Committee of Military Medical Science.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics statement"}}],"article-number":"298"}}