{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:08:55Z","timestamp":1792598935425,"version":"4.5.0"},"reference-count":84,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2018,4,17]],"date-time":"2018-04-17T00:00:00Z","timestamp":1523923200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001168","name":"Cancer Council Queensland","doi-asserted-by":"publisher","award":["1087363"],"award-info":[{"award-number":["1087363"]}],"id":[{"id":"10.13039\/501100001168","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Spermatogenesis is a dynamic process involving self\u2010renewal and differentiation of spermatogonial stem cells, meiosis, and ultimately, the differentiation of haploid spermatids into sperm. Centrosomal protein 55 kDa (CEP55) is necessary for somatic cell abscission during cytokinesis. It facilitates equal segregation of cytoplasmic contents between daughter cells by recruiting endosomal sorting complex required for transport machinery (ESCRT) at the midbody. In germ cells, CEP55, in partnership with testes expressed\u201014 (TEX14) protein, has also been shown to be an integral component of intercellular bridge before meiosis. Various\n                    <jats:italic>in vitro<\/jats:italic>\n                    studies have demonstrated a role for CEP55 in multiple cancers and other diseases. However, its oncogenic potential in vivo remains elusive. To investigate, we generated ubiquitously overexpressing\n                    <jats:italic>Cep55<\/jats:italic>\n                    transgenic (Cep55\n                    <jats:sup>\n                      <jats:italic>Tg<\/jats:italic>\n                      \/\n                      <jats:italic>Tg<\/jats:italic>\n                    <\/jats:sup>\n                    )mice aiming to characterize its oncogenic role in cancer. Unexpectedly, we found that\n                    <jats:italic>\n                      Cep55\n                      <jats:sup>Tg\/Tg<\/jats:sup>\n                    <\/jats:italic>\n                    male mice were sterile and had severe and progressive defects in spermatogenesis related to spermatogenic arrest and lack of spermatids in the testes. In this study, we characterized this male\u2010specific phenotype and showed that excessively high levels of Cep55 results in hyperactivation of PI3K\/protein kinase B (Akt) signaling in testis. In line with this finding, we observed increased phosphorylation of forkhead box protein O1 (FoxO1), and suppression of its nuclear retention, along with the relative enrichment of promyelocytic leukemia zinc finger (PLZF)\u2014positive cells. Independently, we observed that\n                    <jats:italic>Cep55<\/jats:italic>\n                    amplification favored upregulation of ret (\n                    <jats:italic>Ret<\/jats:italic>\n                    ) proto\u2010oncogene and glial\u2010derived neurotrophic factor family receptor a\u20101 (\n                    <jats:italic>Gfra1<\/jats:italic>\n                    ). Consistent with these data, we observed selective down\u2010regulation of genes associated with germ cell differentiation in Cep55\u2010overexpressing testes at postnatal day 10, including early growth response\u20104 (\n                    <jats:italic>Egr4)<\/jats:italic>\n                    and spermatogenesis and oogenesis specific basic helix\u2010loop\u2010helix\u20101 (\n                    <jats:italic>Sohlh1<\/jats:italic>\n                    ). Thus,\n                    <jats:italic>Cep55<\/jats:italic>\n                    amplification leads to a shift toward the initial maintenance of undifferentiated spermatogonia and ultimately results in progressive germ cell loss. Collectively, our findings demonstrate that\n                    <jats:italic>Cep55<\/jats:italic>\n                    overexpression causes change in germ cell proportions and manifests as a Sertoli cell only tubule phenotype, similar to that seen in many azoospermic men.\u2014Sinha, D., Kalimutho, M., Bowles, J., Chan, A.\u2010L., Merriner, D. J., Bain, A. L., Simmons, J. L., Freire, R., Lopez, J. A., Hobbs, R. M., O'Bryan, M. K., Khanna, K. K. Cep55 overexpression causes male\u2010specific sterility in mice by suppressing Foxo1 nuclear retention through sustained activation of PI3K\/Akt signaling. FASEB J. 32, 4984\u20134999 (2018).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201701096rr","type":"journal-article","created":{"date-parts":[[2018,4,23]],"date-time":"2018-04-23T15:51:55Z","timestamp":1524498715000},"page":"4984-4999","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Cep55 overexpression causes male\u2010specific sterility in mice by suppressing Foxo1 nuclear retention through sustained activation of PI3K\/Akt signaling"],"prefix":"10.1096","volume":"32","author":[{"given":"Debottam","family":"Sinha","sequence":"first","affiliation":[{"name":"Queensland Institute of Medical Research (QIMR) Berghofer Medical Research Institute Herston Queensland Australia"},{"name":"School of Natural Sciences Griffith University Nathan Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murugan","family":"Kalimutho","sequence":"additional","affiliation":[{"name":"Queensland Institute of Medical Research (QIMR) Berghofer Medical Research Institute Herston Queensland Australia"},{"name":"School of Natural Sciences Griffith University Nathan Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine","family":"Bowles","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences Institute for Molecular Bioscience The University of Queensland St Lucia Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai-Leen","family":"Chan","sequence":"additional","affiliation":[{"name":"Germline Stem Cell Laboratory Australian Regenerative Medicine Institute and Monash Biomedicine Discovery Institute Department of Anatomy and Developmental Biology Monash University Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Jo","family":"Merriner","sequence":"additional","affiliation":[{"name":"Male Infertility and Germ Cell Biology Laboratory School of Biological Sciences Monash University Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda L.","family":"Bain","sequence":"additional","affiliation":[{"name":"Queensland Institute of Medical Research (QIMR) Berghofer Medical Research Institute Herston Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacinta L.","family":"Simmons","sequence":"additional","affiliation":[{"name":"Queensland Institute of Medical Research (QIMR) Berghofer Medical Research Institute Herston Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raimundo","family":"Freire","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n Hospital Universitario de Canarias Instituto de Tecnolog\u00edas Biom\u00e9dicas Tenerife Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Alejandro","family":"Lopez","sequence":"additional","affiliation":[{"name":"Queensland Institute of Medical Research (QIMR) Berghofer Medical Research Institute Herston Queensland Australia"},{"name":"School of Natural Sciences Griffith University Nathan Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin M.","family":"Hobbs","sequence":"additional","affiliation":[{"name":"Germline Stem Cell Laboratory Australian Regenerative Medicine Institute and Monash Biomedicine Discovery Institute Department of Anatomy and Developmental Biology Monash University Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moira K.","family":"O'Bryan","sequence":"additional","affiliation":[{"name":"Male Infertility and Germ Cell Biology Laboratory School of Biological Sciences Monash University Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kum Kum","family":"Khanna","sequence":"additional","affiliation":[{"name":"Queensland Institute of Medical Research (QIMR) Berghofer Medical Research Institute Herston Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,4,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jemt.20698"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.11.011"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04697"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06129"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2613.1998.00057.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0463.2005.apm_302.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2014.01.019"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M703474200"},{"key":"e_1_2_7_10_1","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1002\/j.1939-4640.2000.tb03408.x","article-title":"All you wanted to know about spermatogonia but were afraid to ask","volume":"21","author":"De Rooij D. 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