{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T15:54:03Z","timestamp":1785772443489,"version":"3.56.0"},"reference-count":70,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,11,29]],"date-time":"2019-11-29T00:00:00Z","timestamp":1574985600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Posttranslational modifications enhance the functional diversity of the proteome by modifying the substrates. The UFM1 cascade is a novel ubiquitin\u2010like modification system. The mutations in\n                    <jats:italic>UFM1<\/jats:italic>\n                    , its E1 (\n                    <jats:italic>UBA5<\/jats:italic>\n                    ) and E2 (\n                    <jats:italic>UFC1<\/jats:italic>\n                    ), have been identified in patients with microcephaly. However, its pathological mechanisms remain unclear. Herein, we observed the disruption of the UFM1 cascade in\n                    <jats:italic>Drosophila<\/jats:italic>\n                    neuroblasts (NBs) decreased the number of NBs, leading to a smaller brain size. The lack of ufmylation in NBs resulted in an increased mitotic index and an extended G2\/M phase, indicating a defect in mitotic progression. In addition, live imaging of the embryos revealed an impaired E3 ligase (\n                    <jats:italic>Ufl1<\/jats:italic>\n                    ) function resulted in premature entry into mitosis and failed cellularization. Even worse, the embryonic lethality occurred as early as within the first few mitotic cycles following the depletion of\n                    <jats:italic>Ufm1.<\/jats:italic>\n                    Knockdown of ufmylation in the fixed embryos exhibited severe phenotypes, including detached centrosomes, defective microtubules, and DNA bridge. Furthermore, we observed that the UFM1 cascade could alter the level of phosphorylation on tyrosine\u201015 of CDK1 (pY15\u2010CDK1), which is a negative regulator of the G2 to M transition. These findings yield unambiguous evidence suggesting that the UFM1 cascade is a microcephaly\u2010causing factor that regulates the progression of the cell cycle at mitosis phase entry.\n                  <\/jats:p>","DOI":"10.1096\/fj.201901751r","type":"journal-article","created":{"date-parts":[[2019,11,29]],"date-time":"2019-11-29T08:18:35Z","timestamp":1575015515000},"page":"1319-1330","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["The UFM1 cascade times mitosis entry associated with microcephaly"],"prefix":"10.1096","volume":"34","author":[{"given":"Li","family":"Yu","sequence":"first","affiliation":[{"name":"Center for Medical Genetics School of Life Sciences Central South University Changsha China"},{"name":"Hunan Key Laboratory of Medical Genetics Central South University Changsha 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