title: N-glycosylation at Asn residues 554 and 566 of E-cadherin affects cell cycle progression through extracellular signal-regulated protein kinase signaling pathway.
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.
authors.affiliation: Key Laboratory of Glycoconjugate Research, Ministry of Health, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Zhao
authors.forename: Lidong
authors.initials: L
authors.lastname: Sun
authors.forename: Liying
authors.initials: L
authors.lastname: Wang
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Xu
authors.forename: Feng
authors.initials: F
authors.lastname: Zhou
authors.forename: Jianmin
authors.initials: J
authors.lastname: Su
authors.forename: Jiawei
authors.initials: J
authors.lastname: Jin
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.forename: Yali
authors.initials: Y
authors.lastname: Hu
authors.forename: Xiliang
authors.initials: X
authors.lastname: Zha
mesh_terms: D019943:Amino Acid Substitution; D001216:Asparagine / Q000737:chemistry; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017931:DNA Primers / Q000235:genetics; D005260:Female; D006031:Glycosylation; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D011134:Polysaccharides / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D015820:Cadherins; D017931:DNA Primers; D011134:Polysaccharides; D011994:Recombinant Proteins; D001216:Asparagine