The p53-p21(Cip1/WAF1) pathway is necessary for cellular senescence induced by the inhibition of protein kinase CKII in human colon cancer cells

• Published in: Molecules and cells Vol. 28; no. 5; p. 489
• Main Authors: Kang, Ji-Young, Kim, Jin Joo, Jang, Seok Young, Bae, Young-Seuk
• Format: Journal Article
• Language: English
• Published: United States 30.11.2009
• Subjects: Casein Kinase II - antagonists & inhibitors; Casein Kinase II - metabolism; Cellular Senescence; Colonic Neoplasms - enzymology; Colonic Neoplasms - genetics; Colonic Neoplasms - metabolism; Cyclin-Dependent Kinase Inhibitor p21 - metabolism; Down-Regulation - genetics; Gene Expression Regulation, Neoplastic; HCT116 Cells; Humans; Phosphorylation; Retinoblastoma Protein - metabolism; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Up-Regulation - genetics
• ISSN: 0219-1032
• DOI: 10.1007/s10059-009-0141-9

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 CKIIalpha 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.