Wang W.-L.Huang H.-C.Kao S.-H.Hsu Y.-C.Wang Y.-T.Li K.-C.Chen Y.-J.SUNG-LIANG YUWang S.-P.Hsiao T.-H.PAN-CHYR YANGHSIAO-CHUN HUANG2020-12-022020-12-0220150950-9232https://www.scopus.com/inward/record.uri?eid=2-s2.0-84928298274&doi=10.1038%2fonc.2014.58&partnerID=40&md5=a729672b09ca03869479cc4d454bdfechttps://scholars.lib.ntu.edu.tw/handle/123456789/523514The transcriptional repressor Slug is best known to control epithelial-mesenchymal transition (EMT) and promote cancer invasion/metastasis. In this study, we demonstrate that Slug is temporally regulated during cell cycle progression. At G1/S transition, cyclin E-cyclin-dependent kinase 2 mediates the phosphorylation of Slug at Ser-54 and Ser-104, resulting in its ubiquitylation and degradation. Non-phosphorylatable Slug is markedly stabilized at G1/S transition compared with wild-type Slug and greatly leads to downregulation of DNA synthesis and checkpoint-related proteins, including TOP1, DNA Ligase IV and Rad17, reduces cell proliferation, delays S-phase progression and contributes to genome instability. Our results indicate that Slug has multifaceted roles in cancer progression by controlling both EMT and genome stability. ? 2015 Macmillan Publishers Limited.[SDGs]SDG3cyclin dependent kinase 2; cyclin E; transcription factor Slug; benzyloxycarbonylleucyl-leucyl-leucine aldehyde; CDK2 protein, human; cyclin dependent kinase 2; cyclin E; leupeptin; snail family transcription factors; transcription factor; Article; cancer growth; cell cycle S phase; cell proliferation; controlled study; DNA synthesis; down regulation; female; G1 phase cell cycle checkpoint; genomic instability; HEK293 cell line; HeLa cell line; human; human cell; metastasis; priority journal; protein degradation; protein expression; protein metabolism; protein phosphorylation; protein stability; real time polymerase chain reaction; U2OS cell line; cell cycle; epithelial mesenchymal transition; gene expression regulation; genetics; metabolism; neoplasm; pathology; phosphorylation; tumor cell line; ubiquitination; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cyclin E; Cyclin-Dependent Kinase 2; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Genomic Instability; HEK293 Cells; HeLa Cells; Humans; Leupeptins; Neoplasms; Phosphorylation; Transcription Factors; Ubiquitinationjournal article10.1038/onc.2014.58246628262-s2.0-84928298274