Full metadata record
DC Field | Value | Language |
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dc.contributor.author | Yang, Eun Jae | - |
dc.contributor.author | Park, Ji Hwan | - |
dc.contributor.author | Cho, Hyun-Ji | - |
dc.contributor.author | Hwang, Jeong-A | - |
dc.contributor.author | Woo, Seung Hwa | - |
dc.contributor.author | Park, Chi Hyun | - |
dc.contributor.author | Kim, Sung Young | - |
dc.contributor.author | Park, Joon Tae | - |
dc.contributor.author | Park, Sang Chul | - |
dc.contributor.author | Hwang, Daehee | - |
dc.contributor.author | Lee, Young-Sam | - |
dc.date.accessioned | 2022-10-19T08:00:01Z | - |
dc.date.available | 2022-10-19T08:00:01Z | - |
dc.date.created | 2022-08-08 | - |
dc.date.issued | 2022-07 | - |
dc.identifier.issn | 2399-3642 | - |
dc.identifier.uri | http://hdl.handle.net/20.500.11750/16910 | - |
dc.description.abstract | The multifaceted nature of senescent cell cycle arrest necessitates the targeting of multiple factors arresting or promoting the cell cycle. We report that co-inhibition of ATM and ROCK by KU-60019 and Y-27632, respectively, synergistically increases the proliferation of human diploid fibroblasts undergoing replicative senescence through activation of the transcription factors E2F1 and FOXM1. Time-course transcriptome analysis identified FOXM1 and E2F1 as crucial factors promoting proliferation. Co-inhibition of the kinases ATM and ROCK first promotes the G2/M transition via FOXM1 activation, leading to accumulation of cells undergoing the G1/S transition via E2F1 activation. The combination of both inhibitors increased this effect more significantly than either inhibitor alone, suggesting synergism. Our results demonstrate a FOXM1- and E2F1-mediated molecular pathway enhancing cell cycle progression in cells with proliferative potential under replicative senescence conditions, and treatment with the inhibitors can be tested for senomorphic effect in vivo. © 2022, The Author(s). | - |
dc.language | English | - |
dc.publisher | Nature Publishing Group | - |
dc.title | Co-inhibition of ATM and ROCK synergistically improves cell proliferation in replicative senescence by activating FOXM1 and E2F1 | - |
dc.type | Article | - |
dc.identifier.doi | 10.1038/s42003-022-03658-5 | - |
dc.identifier.scopusid | 2-s2.0-85134126748 | - |
dc.identifier.bibliographicCitation | Communications Biology, v.5, no.1 | - |
dc.description.isOpenAccess | TRUE | - |
dc.subject.keywordPlus | SECRETORY PHENOTYPE | - |
dc.subject.keywordPlus | DNA-REPLICATION | - |
dc.subject.keywordPlus | LIFE-SPAN | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | TARGET | - |
dc.subject.keywordPlus | INVOLVEMENT | - |
dc.subject.keywordPlus | INTERACTS | - |
dc.subject.keywordPlus | PATHWAYS | - |
dc.subject.keywordPlus | LEVEL | - |
dc.subject.keywordPlus | AXIS | - |
dc.citation.number | 1 | - |
dc.citation.title | Communications Biology | - |
dc.citation.volume | 5 | - |
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