Pim-2 phosphorylation of p21Cip1/WAF1 enhances its stability and inhibits cell proliferation in HCT116 cells
| Autor: | Yandong Zhang, Raymond Reeves, Nancy S. Magnuson, Juan Jenny Gu, Zeping Wang, Christine M. Davitt |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Active Transport Cell Nucleus Endogeny Protein Serine-Threonine Kinases Biology Biochemistry Article Proto-Oncogene Proteins hemic and lymphatic diseases medicine Humans Transgenes Cloning Molecular Phosphorylation RNA Small Interfering Cell Proliferation Cell Nucleus Gene knockdown Protein Stability Cell growth Kinase Cell Biology Cell cycle HCT116 Cells Molecular biology In vitro Cell biology Cell nucleus medicine.anatomical_structure Colorectal Neoplasms |
| Zdroj: | The International Journal of Biochemistry & Cell Biology. 42:1030-1038 |
| ISSN: | 1357-2725 |
| DOI: | 10.1016/j.biocel.2010.03.012 |
| Popis: | Pim-2 kinase is one of the three highly conserved Pim family members which are known to be involved in cell survival and cell proliferation. Here we demonstrate that like Pim-1, Pim-2 also phosphorylates the cell cycle inhibitor p21Cip1/WAF1 (p21) on Thr145 in vitro and in vivo. Overexpression of Pim-2 in HCT116 cells leads to the increased stability of p21 and results in enhanced levels of both exogenous and endogenous p21 proteins. Knockdown of Pim-2 expression via siRNA results in reduced level of endogenous p21, indicating that like Pim-1, Pim-2 is another legitimate p21 kinase. However, Pim-2 has no influence on the nuclear localization of p21 in HCT116 cells. In addition, Pim-2 is able to arrest the cell cycle at G1/S phase and inhibit cell proliferation through phosphorylation of p21 in HCT116 cells. These data suggest that Pim-2 phosphorylation of p21 enhances p21's stability and inhibits cell proliferation in HCT116 cells. |
| Databáze: | OpenAIRE |
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