Dual roles of ERK1/2 in cellular senescence induced by excess thymidine in HeLa cells

Ikuru Kudo, Megumi Nozawa, Kensuke Miki, Yuki Takauji, Atsuki En, Michihiko Fujii, Dai Ayusawa

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)216-223
Number of pages8
JournalExperimental Cell Research
Volume346
Issue number2
DOIs
Publication statusPublished - Aug 15 2016
Externally publishedYes

Fingerprint

Cell Aging
HeLa Cells
Thymidine
Cell Survival
DNA Replication
DNA Damage

Keywords

  • Cellular senescence
  • Chk1
  • DNA damage response
  • ERK1/2
  • Excess thymidine

ASJC Scopus subject areas

  • Cell Biology

Cite this

Dual roles of ERK1/2 in cellular senescence induced by excess thymidine in HeLa cells. / Kudo, Ikuru; Nozawa, Megumi; Miki, Kensuke; Takauji, Yuki; En, Atsuki; Fujii, Michihiko; Ayusawa, Dai.

In: Experimental Cell Research, Vol. 346, No. 2, 15.08.2016, p. 216-223.

Research output: Contribution to journalArticle

Kudo, Ikuru ; Nozawa, Megumi ; Miki, Kensuke ; Takauji, Yuki ; En, Atsuki ; Fujii, Michihiko ; Ayusawa, Dai. / Dual roles of ERK1/2 in cellular senescence induced by excess thymidine in HeLa cells. In: Experimental Cell Research. 2016 ; Vol. 346, No. 2. pp. 216-223.
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