PMID:18235976
| Citation |
Zhao, H, Sun, L, Wang, L, Xu, Z, Zhou, F, Su, J, Jin, J, Yang, Y, Hu, Y and Zha, X (2008) N-glycosylation at Asn residues 554 and 566 of E-cadherin affects cell cycle progression through extracellular signal-regulated protein kinase signaling pathway. Acta Biochim. Biophys. Sin. (Shanghai) 40:140-8 |
|---|---|
| Abstract |
E-cadherin, which has a widely acknowledged role in mediating calcium-dependent cell-cell adhesion between epithelial cells, also functions as a tumor suppressor. The ectodomain of human E-cadherin contains four potential N-glycosylation sites at Asn residues 554, 566, 618, and 633. We investigated the role of E-cadherin N-glycosylation in cell cycle progression by site-directed mutagenesis. We showed previously that all four potential N-glycosylation sites of E-cadherin were N-glycosylated in human breast carcinoma MDA-MB-435 cells. Removal of N-glycan at Asn633 dramatically affected E-cadherin stability. In this study we showed that E-cadherin mutant missing N-glycans at Asn554, Asn566 and Asn618 failed to induce cell cycle arrest in G1 phase and to suppress cell proliferation in comparison with wild-type E-cadherin. Moreover, N-glycans at Asn554 and Asn566, but not at Asn618, seemed to be indispensable for E-cadherin-mediated suppression of cell cycle progression. Removal of N-glycans at either Asn554 or Asn566 of E-cadherin was accompanied with the activation of the extracellular signal-regulated protein kinase signaling pathway. After treatment with PD98059, an inhibitor of the extracellular signal-regulated protein kinase signaling pathway, wild-type E-cadherin transfected MDA-MB-435 and E-cadherin N-glycosylation-deficient mutant transfected MDA-MB-435 cells had equivalent numbers of cells in G1 phase. These findings implied that N-glycosylation might be crucial for E-cadherin-mediated suppression of cell cycle progression. |
| Links | |
| Keywords |
Amino Acid Substitution; Asparagine/chemistry; Base Sequence; Binding Sites/genetics; Breast Neoplasms/genetics; Breast Neoplasms/metabolism; Breast Neoplasms/pathology; Cadherins/chemistry; Cadherins/genetics; Cadherins/metabolism; Cell Cycle/physiology; Cell Line, Tumor; Cell Proliferation; DNA Primers/genetics; Female; Glycosylation; Humans; MAP Kinase Signaling System/physiology; Mutagenesis, Site-Directed; Polysaccharides/chemistry; Recombinant Proteins/chemistry; Recombinant Proteins/genetics; Recombinant Proteins/metabolism; Transfection |
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