title: Dual roles of ERK1/2 in cellular senescence induced by excess thymidine in HeLa cells.
abstract: DNA damage response is crucially involved in cellular senescence. We have previously shown that excess thymidine, which stalls DNA replication forks, induces cellular senescence in human cells, and ERK1/2 play a key role in the induction of it. In this study, we found that Chk1 and ERK1/2 were activated to promote cell survival upon addition of excess thymidine. Knockdown of ERK1/2 activated Chk1, and conversely, knockdown of Chk1 activated ERK1/2, which observations suggested a mechanism for compensatory activation of Chk1 and ERK1/2 in the absence of ERK1/2 and Chk1, respectively. We also found that Chk1 functioned mainly at the onset of cellular senescence, and on the other hand, ERK1/2 functioned for a more extended period to induce cellular senescence. Our findings suggested that Chk1 and ERK1/2 were activated to promote cell survival upon addition of excess thymidine, but prolonged activation of ERK1/2 led to cellular senescence. This implies a pleiotropic effect of ERK1/2 in cellular senescence induced by excess thymidine.
authors.affiliation: Graduate school of Nanobioscience, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama, Kanagawa 236-0027, Japan.
authors.forename: Ikuru
authors.initials: I
authors.lastname: Kudo
authors.affiliation: Graduate school of Nanobioscience, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama, Kanagawa 236-0027, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Nozawa
authors.affiliation: Graduate school of Nanobioscience, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama, Kanagawa 236-0027, Japan; Ichiban Life Corporation, 1-1-7 Horai-cho, Naka-ku, Yokohama, Kanagawa 231-0048, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Miki
authors.affiliation: Graduate school of Nanobioscience, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama, Kanagawa 236-0027, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Takauji
authors.affiliation: Graduate school of Nanobioscience, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama, Kanagawa 236-0027, Japan.
authors.forename: Atsuki
authors.initials: A
authors.lastname: En
authors.affiliation: Graduate school of Nanobioscience, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama, Kanagawa 236-0027, Japan. Electronic address: mifuji@yokohama-cu.ac.jp.
authors.forename: Michihiko
authors.initials: M
authors.lastname: Fujii
authors.affiliation: Graduate school of Nanobioscience, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama, Kanagawa 236-0027, Japan; Ichiban Life Corporation, 1-1-7 Horai-cho, Naka-ku, Yokohama, Kanagawa 231-0048, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Ayusawa
mesh_terms: D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects*; D000071877:Checkpoint Kinase 1 / Q000378:metabolism; D064447:Checkpoint Kinase 2 / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013936:Thymidine / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D064447:Checkpoint Kinase 2; C000605867:CHEK1 protein, human; C578634:CHEK2 protein, human; D000071877:Checkpoint Kinase 1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D013936:Thymidine
keywords: Cellular senescence; Chk1; DNA damage response; ERK1/2; Excess thymidine