2013 Fiscal Year Final Research Report
Mechanism of premature senescence induction through DNA damage responses
| Project/Area Number |
23240124
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Carcinogenesis
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| Research Institution | Nagoya City University |
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Principal Investigator |
NAKANISHI Makoto 名古屋市立大学, 医学(系)研究科(研究院), 教授 (40217774)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Keywords | 癌 / ゲノム / シグナル伝達 / 発現抑制 / 老化 |
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| Research Abstract |
Senescence is a state of permanent growth arrest and is a pivotal part of the anti-tumorigenic barrier in vivo. Although the tumor suppressor activities of p53 and pRb family proteins are essential for the induction of senescence, molecular mechanisms by which these proteins induce senescence are still not clear. Using time-lapse live-cell imaging, we demonstrate here that normal human diploid fibroblasts (HDFs) exposed to various senescence-inducing stimuli undergo a mitosis skip before entry into permanent cell cycle arrest. This mitosis skip is mediated by both p53-dependent premature activation of APC/CCdh1 and pRb family protein-dependent transcriptional suppression of mitotic regulators. Importantly, mitotic skipping is necessary and sufficient for senescence induction. Our findings provide decisive evidence for the molecular basis underlying the induction and maintenance of cellular senescence.
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Research Products
(25 results)
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[Journal Article] Necessary and sufficient role for a mitosis skip in senescence induction2014
Author(s)
Johumra Y, Shimada M, Misaki T, Naiki-Ito A, Miyoshi H, Motoyama N, Ohtani N, Hara E, Nakamura M, Morita A, Takahashi S, Nakanishi M
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Journal Title
Mol.Cell
Volume: (in press)
Peer Reviewed
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[Journal Article] Mammalian-specific H2A variant, H2ABbd, is Involved in Apoptotic Induction via Activation of NF-κB Signaling Pathway2014
Author(s)
Goshima T1, Shimada M, Sharif J, Matsuo H, Misaki T, Johmura Y, Murata K, Koseki H, Nakanishi M
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Journal Title
DOI
Peer Reviewed
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[Journal Article] Uhrf1-dependent H3K23 ubiquitylation couples maintenance DNA methylation and replication2013
Author(s)
Nishiyama A, Yamaguchi L, Sharif J, Johmura Y, Kawamura T, Nakanishi K, Shimamura S, Arita K, Kodama T, Ishikawa F, Koseki H, Nakanishi M
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Journal Title
Nature
Volume: 502(7470)
Pages: 249-53
DOI
Peer Reviewed
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[Journal Article] Involvement of ribonucleotide reductase-M1 in 5-fluorouracil-induced DNA damage in esophageal cancer cell lines2013
Author(s)
Aoki Y, Sakogawa K, Hihara J, Emi M, Hamai Y, Kono K, Shi L, Sun J, Kitao H, Ikura T, Niida H, Nakanishi M, Okada M, Tashiro S
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Journal Title
Int J Oncol
Volume: 42(6)
DOI
Peer Reviewed
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[Journal Article] Chk1 phosphorylates the tumour suppressor Mig-6, regulating the activation of EGF signalling2012
Author(s)
Liu N, Matsumoto M, Kitagawa K, Kotake Y, Suzuki S, Shirasawa S, Nakayama KI, Nakanishi M, Niida H, Kitagawa M
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Journal Title
EMBO J
Volume: 31(10)
Pages: 2365-77
DOI
Peer Reviewed
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[Journal Article] TANK-binding kinase 1 (TBK1) controls cell survival through PAI-2/serpinB2 and transglutaminase 22012
Author(s)
Delhase M, Kim SY, Lee H, Naiki-Ito A, Chen Y, Ahn ER, Murata K, Kim SJ, Lautsch N, Kobayashi KS, Shirai T, Karin M, Nakanishi M
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Journal Title
Proc Natl Acad Sci U S A
Volume: 109(4)
Pages: E177-86
DOI
Peer Reviewed
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[Journal Article]2011
Author(s)
Nakanishi M
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Journal Title
Cell cycle. Rinsho Ketsueki
Volume: 52(10)
Pages: 1660-8
Peer Reviewed
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[Journal Article] Easy-to-use phylogenetic analysis system for hepatitis B virus infection2011
Author(s)
Sugiyama M, Inui A, Shin-I T, Komatsu H, Mukaide M, Masaki N, Murata K, Ito K, Nakanishi M, Fujisawa T, Mizokami M
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Journal Title
Hepatol Res
Volume: 41(10)
Pages: 936-945
DOI
Peer Reviewed
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