The p53-p21Cip1/WAF1 pathway is necessary for cellular senescence induced by the inhibition of protein kinase CKII in human colon cancer cells
| Autor: | Seok Young Jang, Jin Joo Kim, Ji-Young Kang, Young-Seuk Bae |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Senescence Protein Kinase CKII Down-Regulation Biology Retinoblastoma Protein Mediator Downregulation and upregulation Transcription (biology) medicine Humans Phosphorylation Casein Kinase II Fibroblast Molecular Biology Cellular Senescence Cell Biology General Medicine HCT116 Cells Molecular biology Up-Regulation Staining Gene Expression Regulation Neoplastic medicine.anatomical_structure Cell culture Colonic Neoplasms Tumor Suppressor Protein p53 |
| Zdroj: | Molecules and Cells. 28:489-494 |
| ISSN: | 0219-1032 1016-8478 |
| DOI: | 10.1007/s10059-009-0141-9 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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