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Co-inhibition of ATM and ROCK synergistically improves cell proliferation in replicative senescence by activating FOXM1 and E2F1
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 | 2022-10-11T00:25:49Z | - |
dc.date.available | 2022-10-11T00:25:49Z | - |
dc.date.created | 2022-07-28 | - |
dc.date.issued | 2022-12 | - |
dc.identifier.citation | Communications Biology, Vol.5 No.1, p. 702 | - |
dc.identifier.issn | 2399-3642 | - |
dc.identifier.uri | https://hdl.handle.net/10371/185636 | - |
dc.description.abstract | © 2022, The Author(s).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. | - |
dc.language | 영어 | - |
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.citation.journaltitle | Communications Biology | - |
dc.identifier.wosid | 000825483800004 | - |
dc.identifier.scopusid | 2-s2.0-85134126748 | - |
dc.citation.number | 1 | - |
dc.citation.startpage | 702 | - |
dc.citation.volume | 5 | - |
dc.description.isOpenAccess | N | - |
dc.contributor.affiliatedAuthor | Hwang, Daehee | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
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