The p53-p21Cip1/WAF1 Pathway Is Necessary for Cellular Senescence Induced by the Inhibition of Protein Kinase CKII in Human Colon Cancer Cells

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 p21Cip1/WAF1 in senescence development induced by CKII inhibition using wild-type, isogenic p53-/-...

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Bibliographic Details
Published in:Molecules and cells 2009, 28(5), , pp.489-494
Main Authors: Kang, Ji-Young, Kim, Jin Joo, Jang, Seok Young, Bae, Young-Seuk
Format: Article
Language:English
Subjects:
Biochemistry
Biomedical and Life Sciences
Biomedicine
Biotechnology
Cell Biology
Communication
human colon cancer cell
Life Sciences
p21Cip1/WAF1
p53
protein kinase CKII
senescence
생물학
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Summary: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 p21Cip1/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 β-galactosidase activity in wild-type HCT116 cells treated with CKII inhibitor or CKIIα siRNA, but this response was almost abolished in p53- or p21Cip1/WAF1-null cells. Increased cellular levels of p53 and p21Cip1/WAF1 protein occurred with the inhibition of CKII. CKII inhibition upregulated p53 and p21Cip1/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-p21Cip1/WAF1 pathway acts as a major mediator of cellular senescence induced by CKII inhibition.
ISSN:1016-8478
0219-1032
DOI:10.1007/s10059-009-0141-9