Back to Search
Start Over
Rock2 regulates Cdc25A through ubiquitin proteasome system in hepatocellular carcinoma cells
- Source :
- Experimental cell research. 318(16)
- Publication Year :
- 2011
-
Abstract
- Rho-associated coiled-coil containing protein kinase 2 (Rock2) belongs to a family of serine/threonine kinases which are actived via interaction with Rho GTPases. Recently, overexpression of Rock2 has been demonstrated in human hepatocellular carcinoma (HCC), but the potential role of Rock2 in tumorigenesis remains unclear. Cdc25A acts as a key checkpoint during the G1/S phase and has also been found to be overexpressed in HCC. Here, we report that Rock2 regulates cell cycle progression via ubiquitination of Cdc25A in HCC. In HCC tissues, Rock2 and Cdc25A were aberrantly upregulated and revealed a significantly positive correlation. Knockdown of Rock2 inhibited HCC cell growth and promoted cell-cycle arrest at the G1/S phase via regulation of Cdc25A. When cells were exposed to DNA damage, Rock2 increased cell survival by regulating Cdc25A. Co-immunoprecipitation and immunofluorescence analyses indicated that Rock2 regulated Cdc25A via direct binding. Furthermore, knockdown of Rock2 activated Cdc25A ubiquitination and promoted its degradation. Our results defined a role for Rock2 in modulation of Cdc25A ubiquitination, indicating a novel mechanism of Cdc25A regulation and a potential function for Rock2 in the development of HCC.
- Subjects :
- CDC25A
Proteasome Endopeptidase Complex
Carcinoma, Hepatocellular
Ultraviolet Rays
Biology
Ubiquitin
Cell Line, Tumor
Humans
cdc25 Phosphatases
ROCK2
RNA, Small Interfering
Protein kinase A
Cell Proliferation
rho-Associated Kinases
Cell growth
Kinase
X-Rays
Liver Neoplasms
Ubiquitination
Cell Biology
G1 Phase Cell Cycle Checkpoints
digestive system diseases
Cell biology
Gene Expression Regulation, Neoplastic
Proteasome
Gene Knockdown Techniques
Cancer research
biology.protein
Signal transduction
DNA Damage
Protein Binding
Signal Transduction
Subjects
Details
- ISSN :
- 10902422
- Volume :
- 318
- Issue :
- 16
- Database :
- OpenAIRE
- Journal :
- Experimental cell research
- Accession number :
- edsair.doi.dedup.....5623b5ca1bfb6d6b3d1b804be0c43b51