Cyclin-dependent kinase 1-mediated phosphorylation of protein kinase N1 promotes anchorage-independent growth and migration
| Autor: | Renya Zeng, Shuping Yang, Jixin Dong, Zhan Wang, Xinyue Li, Yuanhong Chen |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Carcinogenesis environment and public health 03 medical and health sciences 0302 clinical medicine Cell Movement CDC2 Protein Kinase Humans Protein phosphorylation Phosphorylation Kinase activity education Mitosis Protein Kinase C Protein kinase C Cell Proliferation education.field_of_study Cyclin-dependent kinase 1 Kinase Chemistry Cell Biology Cell biology Protein kinase N1 enzymes and coenzymes (carbohydrates) HEK293 Cells 030104 developmental biology 030220 oncology & carcinogenesis HeLa Cells |
| Zdroj: | Cellular Signalling. 69:109546 |
| ISSN: | 0898-6568 |
| DOI: | 10.1016/j.cellsig.2020.109546 |
| Popis: | Protein kinase N1 (PKN1) is a member of the protein kinase C superfamily. Aberrations of PKN1 kinase activity are involved in several human pathological processes, including cancer. We found that PKN family proteins (PKN1/2/3) are phosphorylated in response to antitubulin drug-induced mitotic arrest. We identified cyclin-dependent kinase 1 (CDK1) as the corresponding kinase for PKN protein phosphorylation. CDK1 phosphorylates PKN1 at S533, S537, S562, and S916 in vitro and in cells during drug-induced mitotic arrest. Immunofluorescence staining further confirmed that PKN1 phosphorylation occurs during normal mitosis in a CDK1-dependent manner. Knockdown of PKN1 significantly inhibited anchorage-independent growth and migration without affecting proliferation in multiple cancer cell lines. We further showed that mitotic phosphorylation is essential for PKN1's oncogenic function, as the non-phosphorylatable mutant PKN1-4A failed to rescue anchorage-independent growth and migration in PKN1-knockdown cells. Thus, our findings reveal a novel regulatory mechanism for PKN1 in mitosis and its role in tumorigenesis. |
| Databáze: | OpenAIRE |
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