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http://dx.doi.org/10.1007/s10059-009-0141-9

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)
Publication Information
Molecules and Cells / v.28, no.5, 2009 , pp. 489-494 More about this Journal
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
human colon cancer cell; $p21^{Cip1/WAF1}$; p53; protein kinase CKII; senescence;
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