{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T13:32:46Z","timestamp":1783603966604,"version":"3.55.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2007,10,26]],"date-time":"2007-10-26T00:00:00Z","timestamp":1193356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Fukushima Medical University"},{"DOI":"10.13039\/501100004330","name":"Smoking Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004330","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Survivin, which is a member of the inhibitor of apoptosis protein family, was found originally in immature cells and cancer cells but not in non-neoplastic adult tissues. The subsequent identification of four other alternative splice variants that possess distinct functions and localizations suggested the diverse roles of survivin isoforms. An unspecified isoform of survivin was found recently to be induced in terminally differentiated neutrophils by cytokines that prolong the neutrophil lifespan, such as GM-CSF and G-CSF, suggesting the importance of survivin in blocking apoptosis in neutrophils. To examine the mechanism by which survivin inhibits neutrophil apoptosis, we attempted to induce survivin by GM-CSF\/G-CSF in an HL60 cell line that was differentiated into neutrophils by all-trans retinoic acid and DMSO and freshly isolated human neutrophils. The antiapoptotic isoform \u201cSurvivin,\u201d which was decreased during differentiation, was re-induced by GM-CSF in neutrophil-like, differentiated HL60. In contrast, in normal neutrophils, survivin mRNA was observed to increase spontaneously after 24 h incubation, and no additional elevation was induced by GM-CSF\/G-CSF, which exerted their antiapoptotic effects on the neutrophils in 6 h, despite the lack of survivin induction. PCR and Western blotting detected Survivin-2\u03b1, a dominant-negative of antiapoptotic Survivin, with no other isoforms in the freshly isolated or incubated neutrophils. Our study revealed that the expressed isoforms and the response to GM-CSF were different between the HL60-derived and normal neutrophils, which predominantly expressed Survivin-2\u03b1, not likely involved in apoptosis inhibition by GM-CSF\/G-CSF.<\/jats:p>","DOI":"10.1189\/jlb.0507282","type":"journal-article","created":{"date-parts":[[2007,10,26]],"date-time":"2007-10-26T23:46:58Z","timestamp":1193442418000},"page":"393-400","source":"Crossref","is-referenced-by-count":18,"title":["Terminally differentiated neutrophils predominantly express Survivin-2\u03b1, a dominant-negative isoform of Survivin"],"prefix":"10.1093","volume":"83","author":[{"given":"Huiyuan","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Fukushima Medical University School of Medicine , Fukushima , Japan"},{"name":"Department of Pharmacology, China Medical University , Shenyang , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yayoi","family":"Shikama","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Fukushima Medical University School of Medicine , Fukushima , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isao","family":"Matsuoka","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Fukushima Medical University School of Medicine , Fukushima , Japan"},{"name":"Laboratory of Pharmacology, Faculty of Pharmacy, Takasaki University of Health and Welfare , Takasaki , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junko","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Fukushima Medical University School of Medicine , Fukushima , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2007,10,26]]},"reference":[{"key":"2023033006291005200_","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1172\/JCI113970","article-title":"Macrophage phagocytosis of aging neutrophils in inflammation. Programmed cell death in the neutrophil leads to its recognition by macrophages","volume":"83","author":"Savill","year":"1989","journal-title":"J. Clin. Invest."},{"key":"2023033006291005200_","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1002\/jlb.54.4.283","article-title":"Inhibition of apoptosis and prolongation of neutrophil functional longevity by inflammatory mediators","volume":"54","author":"Lee","year":"1993","journal-title":"J. Leukoc. Biol."},{"key":"2023033006291005200_","doi-asserted-by":"crossref","first-page":"2920","DOI":"10.1182\/blood.V80.11.2920.2920","article-title":"Prolongation of survival of human polymorphonuclear neutrophils by granulocyte-macrophage colony-stimulating factor is caused by inhibition of programmed cell death","volume":"80","author":"Brach","year":"1992","journal-title":"Blood"},{"key":"2023033006291005200_","doi-asserted-by":"crossref","first-page":"2495","DOI":"10.1182\/blood.V92.7.2495","article-title":"Mcl-1 expression in human neutrophils: regulation by cytokines and correlation with cell survival","volume":"92","author":"Moulding","year":"1998","journal-title":"Blood"},{"key":"2023033006291005200_","doi-asserted-by":"crossref","first-page":"7486","DOI":"10.4049\/jimmunol.166.12.7486","article-title":"Cooperative regulation of Mcl-1 by Janus kinase\/stat and phosphatidylinositol 3-kinase contribute to granulocyte-macrophage colony-stimulating factor-delayed apoptosis in human neutrophils","volume":"166","author":"Epling-Burnette","year":"2001","journal-title":"J. Immunol."},{"key":"2023033006291005200_","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1006\/bbrc.1998.9155","article-title":"A1 is a constitutive and inducible Bcl-2 homologue in mature human neutrophils","volume":"249","author":"Chuang","year":"1998","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2023033006291005200_","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1189\/jlb.70.5.783","article-title":"BCL-2 family expression in human neutrophils during delayed and accelerated apoptosis","volume":"70","author":"Moulding","year":"2001","journal-title":"J. Leukoc. Biol."},{"key":"2023033006291005200_","doi-asserted-by":"crossref","first-page":"3106","DOI":"10.1182\/blood.V93.9.3106.409k36_3106_3115","article-title":"Bcl-Xl- and Bax-\u03b1-mediated regulation of apoptosis of human neutrophils via caspase-3","volume":"93","author":"Weinmann","year":"1999","journal-title":"Blood"},{"key":"2023033006291005200_","doi-asserted-by":"crossref","first-page":"13330","DOI":"10.1073\/pnas.96.23.13330","article-title":"Cytokine-mediated Bax deficiency and consequent delayed neutrophil apoptosis: a general mechanism to accumulate effector cells in inflammation","volume":"96","author":"Dibbert","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023033006291005200_","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1182\/blood-2002-05-1505","article-title":"Expression of the inhibitor of apoptosis (IAP) family members in human neutrophils: up-regulation of cIAP2 by granulocyte colony-stimulating factor and overexpression of cIAP2 in chronic neutrophilic leukemia","volume":"101","author":"Hasegawa","year":"2003","journal-title":"Blood"},{"key":"2023033006291005200_","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/nrm830","article-title":"IAP proteins: blocking the road to death\u2019s door","volume":"3","author":"Salvesen","year":"2002","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2023033006291005200_","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1038\/nm0897-917","article-title":"A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma","volume":"3","author":"Ambrosini","year":"1997","journal-title":"Nat. Med."},{"key":"2023033006291005200_","first-page":"43","article-title":"Developmentally regulated expression of the novel cancer anti-apoptosis gene survivin in human and mouse differentiation","volume":"152","author":"Adida","year":"1998","journal-title":"Am. J. Pathol."},{"key":"2023033006291005200_","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/25141","article-title":"Control of apoptosis and mitotic spindle checkpoint by survivin","volume":"396","author":"Li","year":"1998","journal-title":"Nature"},{"key":"2023033006291005200_","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1083\/jcb.151.7.1575","article-title":"Human survivin is a kinetochore-associated passenger protein","volume":"151","author":"Skoufias","year":"2000","journal-title":"J. Cell Biol."},{"key":"2023033006291005200_","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1242\/jcs.115.3.575","article-title":"Survivin exists in immunochemically distinct subcellular pools and is involved in spindle microtubule function","volume":"115","author":"Fortugno","year":"2002","journal-title":"J. Cell Sci."},{"key":"2023033006291005200_","first-page":"167","article-title":"Radiosensitization, after a combined treatment of survivin siRNA and irradiation, is correlated with the activation of caspases 3 and 7 in a wt-p53 sarcoma cell line, but not in a mt-p53 sarcoma cell line","volume":"13","author":"Kappler","year":"2005","journal-title":"Oncol. Rep."},{"key":"2023033006291005200_","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1158\/1535-7163.MCT-05-0132","article-title":"Silencing of survivin gene by small interfering RNAs produces supra-additive growth suppression in combination with 17-allylamino-17-demethoxygeldanamycin in human prostate cancer cells","volume":"5","author":"Paduano","year":"2006","journal-title":"Mol. Cancer Ther."},{"key":"2023033006291005200_","first-page":"2805","article-title":"A novel antisense oligonucleotide targeting survivin expression induces apoptosis and sensitizes lung cancer cells to chemotherapy","volume":"60","author":"Olie","year":"2000","journal-title":"Cancer Res."},{"key":"2023033006291005200_","doi-asserted-by":"crossref","first-page":"23130","DOI":"10.1074\/jbc.M300957200","article-title":"Direct interaction between survivin and Smac\/DIABLO is essential for the anti-apoptotic activity of survivin during taxol-induced apoptosis","volume":"278","author":"Song","year":"2003","journal-title":"J. Biol. Chem."},{"key":"2023033006291005200_","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1002\/jcp.20634","article-title":"Survivin study: An update of \u201cWhat is the next wave?\u201d","volume":"208","author":"Li","year":"2006","journal-title":"J. Cell. Physiol."},{"key":"2023033006291005200_","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1476-4598-4-11","article-title":"Survivin 2\u03b1: a novel Survivin splice variant expressed in human malignancies","volume":"4","author":"Caldas","year":"2005","journal-title":"Mol. Cancer"},{"key":"2023033006291005200_","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1038\/sj.bjc.6602340","article-title":"Role of survivin and its splice variants in tumorigenesis","volume":"92","author":"Li","year":"2005","journal-title":"Br. J. Cancer"},{"key":"2023033006291005200_","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1182\/blood.V95.4.1435.004k01_1435_1442","article-title":"Three differentially expressed survivin cDNA variants encode proteins with distinct antiapoptotic functions","volume":"95","author":"Conway","year":"2000","journal-title":"Blood"},{"key":"2023033006291005200_","first-page":"6097","article-title":"Survivin-Ex3 and survivin-2B: two novel splice variants of the apoptosis inhibitor survivin with different antiapoptotic properties","volume":"59","author":"Mahotka","year":"1999","journal-title":"Cancer Res."},{"key":"2023033006291005200_","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.1038\/sj.onc.1208350","article-title":"Survivin splice variants regulate the balance between proliferation and cell death","volume":"24","author":"Caldas","year":"2005","journal-title":"Oncogene"},{"key":"2023033006291005200_","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.lungcan.2005.03.037","article-title":"Differential expression of survivin-2B and survivin-Ex3 is inversely associated with disease relapse and patient survival in non-small-cell lung cancer (NSCLC)","volume":"49","author":"Ling","year":"2005","journal-title":"Lung Cancer"},{"key":"2023033006291005200_","doi-asserted-by":"crossref","first-page":"7545","DOI":"10.1038\/sj.onc.1208038","article-title":"An alternatively spliced survivin variant is positively regulated by p53 and sensitizes leukemia cells to chemotherapy","volume":"23","author":"Zhu","year":"2004","journal-title":"Oncogene"},{"key":"2023033006291005200_","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1016\/j.bbrc.2003.12.178","article-title":"Identification of a novel splice variant of the human anti-apoptopsis gene survivin","volume":"314","author":"Badran","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2023033006291005200_","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1182\/blood.V98.7.2091","article-title":"Regulation of the inhibitor-of-apoptosis family member survivin in normal cord blood and bone marrow CD34(+) cells by hematopoietic growth factors: implication of survivin expression in normal hematopoiesis","volume":"98","author":"Fukuda","year":"2001","journal-title":"Blood"},{"key":"2023033006291005200_","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1084\/jem.20031588","article-title":"Essential role of survivin, an inhibitor of apoptosis protein, in T cell development, maturation, and homeostasis","volume":"199","author":"Xing","year":"2004","journal-title":"J. Exp. Med."},{"key":"2023033006291005200_","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1182\/blood-2006-02-003749","article-title":"Dissecting the role of endothelial Survivin Ex3 in angiogenesis","volume":"109","author":"Caldas","year":"2007","journal-title":"Blood"},{"key":"2023033006291005200_","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1182\/blood-2003-05-1756","article-title":"Survivin regulates hematopoietic progenitor cell proliferation through p21WAF1\/Cip1-dependent and -independent pathways","volume":"103","author":"Fukuda","year":"2004","journal-title":"Blood"},{"key":"2023033006291005200_","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1084\/jem.20032033","article-title":"Inflammation-associated cell cycleindependent block of apoptosis by survivin in terminally differentiated neutrophils","volume":"199","author":"Altznauer","year":"2004","journal-title":"J. Exp. Med."},{"key":"2023033006291005200_","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/0003-2697(87)90021-2","article-title":"Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction","volume":"162","author":"Chomczynski","year":"1987","journal-title":"Anal. Biochem."},{"key":"2023033006291005200_","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1182\/blood-2004-12-4589","article-title":"Indole-3-carbinol suppresses NF-\u03baB and I\u03baB\u03b1 kinase activation, causing inhibition of expression of NF-\u03baB-regulated antiapoptotic and metastatic gene products and enhancement of apoptosis in myeloid and leukemia cells","volume":"106","author":"Takada","year":"2005","journal-title":"Blood"},{"key":"2023033006291005200_","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1172\/JCI200422222","article-title":"Mitochondrial survivin inhibits apoptosis and promotes tumorigenesis","volume":"114","author":"Dohi","year":"2004","journal-title":"J. Clin. Invest."},{"key":"2023033006291005200_","first-page":"5071","article-title":"Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer","volume":"58","author":"Kawasaki","year":"1998","journal-title":"Cancer Res."},{"key":"2023033006291005200_","first-page":"127","article-title":"Expression of survivin and its relationship to loss of apoptosis in breast carcinomas","volume":"6","author":"Tanaka","year":"2000","journal-title":"Clin. Cancer Res."},{"key":"2023033006291005200_","first-page":"3131","article-title":"Inducible nitric oxide synthase and survivin messenger RNA expression in hepatocellular carcinoma","volume":"8","author":"Ikeguchi","year":"2002","journal-title":"Clin. Cancer Res."}],"container-title":["Journal of Leukocyte Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1189%2Fjlb.0507282","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/83\/2\/393\/49636532\/jlb0393.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/83\/2\/393\/49636532\/jlb0393.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,14]],"date-time":"2023-05-14T14:49:56Z","timestamp":1684075796000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jleukbio\/article\/83\/2\/393\/6975567"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,10,26]]},"references-count":40,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2007,10,26]]},"published-print":{"date-parts":[[2008,2,1]]}},"URL":"https:\/\/doi.org\/10.1189\/jlb.0507282","relation":{},"ISSN":["0741-5400","1938-3673"],"issn-type":[{"value":"0741-5400","type":"print"},{"value":"1938-3673","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2008,2]]},"published":{"date-parts":[[2007,10,26]]}}}