{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T04:38:54Z","timestamp":1790224734522,"version":"4.1.0"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,6,22]],"date-time":"2020-06-22T00:00:00Z","timestamp":1592784000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,6,22]],"date-time":"2020-06-22T00:00:00Z","timestamp":1592784000000},"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>\n                  <jats:p>\n                    FZR1\/CDH1 is an activator of Anaphase promoting complex\/Cyclosome (APC\/C), best known for its role as E3 ubiquitin ligase that drives the cell cycle. APC\/C activity is regulated by CDK-mediated phosphorylation of FZR1 during mitotic cell cycle. Although the critical role of FZR1 phosphorylation has been shown mainly in yeast and\n                    <jats:italic>in vitro<\/jats:italic>\n                    cell culture studies, its biological significance in mammalian tissues\n                    <jats:italic>in vivo<\/jats:italic>\n                    remained elusive. Here, we examined the\n                    <jats:italic>in vivo<\/jats:italic>\n                    role of FZR1 phosphorylation using a mouse model, in which non-phosphorylatable substitutions were introduced in the putative CDK-phosphorylation sites of FZR1. Although ablation of FZR1 phosphorylation did not show substantial consequences in mouse somatic tissues, it led to severe testicular defects resulting in male infertility. In the absence of FZR1 phosphorylation, male juvenile germ cells entered meiosis normally but failed to enter meiosis II or form differentiated spermatids. In aged testis, male mutant germ cells were overall abolished, showing Sertoli cell-only phenotype. In contrast, female mutants showed apparently normal progression of meiosis. The present study demonstrated that phosphorylation of FZR1 is required for temporal regulation of APC\/C activity at meiosis II entry, and for maintenance of spermatogonia, which raised an insight into the sexual dimorphism of FZR1-regulation in germ cells.\n                  <\/jats:p>","DOI":"10.1038\/s41598-020-67116-0","type":"journal-article","created":{"date-parts":[[2020,6,22]],"date-time":"2020-06-22T06:03:36Z","timestamp":1592805816000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Phosphorylation of the Anaphase Promoting Complex activator FZR1\/CDH1 is required for Meiosis II entry in mouse male germ cell"],"prefix":"10.1038","volume":"10","author":[{"given":"Nobuhiro","family":"Tanno","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Kuninaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayoko","family":"Fujimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazumasa","family":"Takemoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaho","family":"Okamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Takeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimi","family":"Araki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatake","family":"Araki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideyuki","family":"Saya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei-ichiro","family":"Ishiguro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,6,22]]},"reference":[{"issue":"Pt 12","key":"67116_CR1","doi-asserted-by":"crossref","first-page":"2401","DOI":"10.1242\/jcs.02937","volume":"119","author":"C Acquaviva","year":"2006","unstructured":"Acquaviva, C. & Pines, J. The anaphase-promoting complex\/cyclosome: APC\/C. J Cell Sci 119(Pt 12), 2401\u20134 (2006).","journal-title":"J Cell Sci"},{"issue":"6","key":"67116_CR2","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1101\/gad.14.6.655","volume":"14","author":"CM Pfleger","year":"2000","unstructured":"Pfleger, C. M. & Kirschner, M. W. The KEN box: an APC recognition signal distinct from the D box targeted by Cdh1. Genes Dev 14(6), 655\u201365 (2000).","journal-title":"Genes Dev"},{"issue":"17","key":"67116_CR3","doi-asserted-by":"crossref","first-page":"4500","DOI":"10.1093\/emboj\/cdf452","volume":"21","author":"A Zur","year":"2002","unstructured":"Zur, A. & Brandeis, M. Timing of APC\/C substrate degradation is determined by fzy\/fzr specificity of destruction boxes. EMBO J 21(17), 4500\u201310 (2002).","journal-title":"EMBO J"},{"issue":"9","key":"67116_CR4","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1038\/nrm1988","volume":"7","author":"JM Peters","year":"2006","unstructured":"Peters, J. M. The anaphase promoting complex\/cyclosome: a machine designed to destroy. Nat Rev Mol Cell Biol 7(9), 644\u201356 (2006).","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"10","key":"67116_CR5","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1038\/sj.embor.7400772","volume":"7","author":"A Reis","year":"2006","unstructured":"Reis, A. et al. The CRY box: a second APCcdh1-dependent degron in mammalian cdc20. EMBO Rep 7(10), 1040\u20135 (2006).","journal-title":"EMBO Rep"},{"issue":"1","key":"67116_CR6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/onc.2009.325","volume":"29","author":"R Wasch","year":"2010","unstructured":"Wasch, R., Robbins, J. A. & Cross, F. R. 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