Rock2 regulates Cdc25A through ubiquitin proteasome system in hepatocellular carcinoma cells.
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.
Department of Hepatobiliary Surgery, Second Affiliated Hospital of Nanchang University, Jiangxi Province, China.
Tiande
T
Liu
Xin
X
Yu
Guohui
G
Li
Rongfa
R
Yuan
Qingnuo
Q
Wang
Ping
P
Tang
Linquan
L
Wu
Xiuxia
X
Liu
Xiaogang
X
Peng
Jianghua
J
Shao
D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004249:DNA Damage; D059585:G1 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D025801:Ubiquitin; D054875:Ubiquitination; D014466:Ultraviolet Rays; D014965:X-Rays; D020687:cdc25 Phosphatases / Q000235:genetics* / Q000378:metabolism; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
D034741:RNA, Small Interfering; D025801:Ubiquitin; C515852:ROCK2 protein, human; D054460:rho-Associated Kinases; C517004:CDC25A protein, human; D020687:cdc25 Phosphatases; D046988:Proteasome Endopeptidase Complex