Integrin beta(1A) upregulates p27 protein amount at the post-translational level in human hepatocellular carcinoma cell line SMMC-7721.
Integrins mediate many fundamental cellular processes by binding to components of the extracellular matrix. We showed previously that integrin beta(1A) could inhibit cell proliferation. Integrin beta(1A) stimulated the promoter activity of p21(cip1) and enhanced its transcription in SMMC-7721 cells. In this study, we demonstrated that integrin beta(1A) upregulated p27(kip1) at the post-translational level in SMMC-7721 cells. Our results showed that integrin beta(1A) increased the p27 protein amount, both in cytoplasm and nucleus, but did not affect the p27 mRNA amount. Cycloheximide treatment experiment revealed that the half-life of p27 protein was prolonged in integrin beta1A overexpressing cells, indicating that integrin beta(1A) inhibited the degradation of p27 protein. Our data also provided evidence that both the proteasome and calpain were involved in the degradation of p27 protein in SMMC-7721 cells. Integrin beta(1A) decreased the Skp2 expression and repressed the activity of calpain during G1 phase in SMMC-7721 cells. Taken together, these results indicated that integrin beta(1A) might upregulate the protein amount of p27 through repressing Skp2-dependent proteasome degradation and calpain-mediated proteolysis in SMMC-7721 cells.
Fu
Yi
Y
Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Wang
Li-Ying
LY
Liang
Yu-Long
YL
Jin
Jia-Wei
JW
Fang
Zheng-Yu
ZY
Zha
Xi-Liang
XL
D002154:Calpain / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000378:metabolism*; D045744:Cell Line, Tumor; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism*; D016193:G1 Phase; D006207:Half-Life; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D008113:Liver Neoplasms / Q000201:enzymology / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism; D015854:Up-Regulation
D019012:Integrin beta1; D012333:RNA, Messenger; D044786:S-Phase Kinase-Associated Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D002154:Calpain; D046988:Proteasome Endopeptidase Complex