Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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The p53-p21Cip1/WAF1 Pathway Is Necessary for Cellular Senescence Induced by the Inhibition of Protein Kinase CKII in Human Colon Cancer Cells

  • Kang, Ji-Young (School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University) ;
  • Kim, Jin Joo (School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University) ;
  • Jang, Seok Young (School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University) ;
  • Bae, Young-Seuk (School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University)
  • Received : 2009.05.06
  • Accepted : 2009.09.07
  • Published : 2009.11.30
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Abstract

We have previously shown that the down-regulation of protein kinase CKII activity is tightly associated with cellular senescence of human fibroblast IMR-90 cells. Here, we examined the roles of p53 and $p21^{Cip1/WAF1}$ in senescence development induced by CKII inhibition using wild-type, isogenic p53-/- and isogenic p21-/- HCT116 human colon cancer cell lines. A senescent marker appeared after staining for senescence-associated ${\beta}$-galactosidase activity in wild-type HCT116 cells treated with CKII inhibitor or $CKII{\alpha}$ siRNA, but this response was almost abolished in p53- or $p21^{Cip1/WAF1}$-null cells. Increased cellular levels of p53 and $p21^{Cip1/WAF1}$ protein occurred with the inhibition of CKII. CKII inhibition upregulated p53 and $p21^{Cip1/WAF1}$ expression at post-transcriptional level and transcription level, respectively. RB phosphorylation significantly decreased in cells treated with CKII inhibitor. Taken together, this study shows that the activation of the $p53-p21^{Cip1/WAF1}$ pathway acts as a major mediator of cellular senescence induced by CKII inhibition.

Keywords

Acknowledgement

Supported by : Kyungpook National University

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