Identification of the Motif in Versican G3 Domain That Plays a Dominant-negative Effect on Astrocytoma Cell Proliferation through Inhibiting Versican Secretion and Binding
| Autor: | Lee Cyn Ang, Yaou Zhang, Chris Kiani, Mark E. Adams, Liwen Chen, Vivian Lee, Peng-Sheng Zheng, Yaojiong Wu, Frouz F. Paiwand, Liu Cao, Burton B. Yang |
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| Rok vydání: | 2001 |
| Předmět: |
DNA
Complementary Cell division Amino Acid Motifs Blotting Western Genetic Vectors Cell Astrocytoma Transfection Binding Competitive Biochemistry Versicans Epidermal growth factor Proto-Oncogene Proteins Tumor Cells Cultured medicine Animals Cyclin D1 Lectins C-Type Secretion neoplasms Molecular Biology Cells Cultured Genes Dominant biology Brain Neoplasms Reverse Transcriptase Polymerase Chain Reaction Cell growth Cell Cycle Cyclin-Dependent Kinase 4 Glioma Cell Biology Cell cycle Cyclin-Dependent Kinases Recombinant Proteins Protein Structure Tertiary Cell biology carbohydrates (lipids) medicine.anatomical_structure Chondroitin Sulfate Proteoglycans COS Cells Mutation biology.protein Versican Proteoglycans Cell Division Cell Nucleolus Gene Deletion Protein Binding |
| Zdroj: | Journal of Biological Chemistry. 276:14178-14186 |
| ISSN: | 0021-9258 |
| Popis: | This study was designed to investigate the mechanisms by which mutant versican constructs play a dominant-negative effect on astrocytoma cell proliferation. Although a mini-versican or a versican G3 construct promoted growth of U87 astrocytoma cells, a mini-versican lacking epidermal growth factor (EGF) motifs (versicanDeltaEGF) and a G3 mutant (G3DeltaEGF) exerted a dominant-negative effect on cell proliferation. G3DeltaEGF-transfected cells formed smaller colonies, arrested cell cycle at G(1) phase, inhibited expression of cell cycle proteins cdk4 and cyclin D1, and contained multiple nucleoli. In cell surface binding assays, G3 products expressed in COS-7 cells and bacteria bound to U87 cell surface. G3DeltaEGF products exhibited decreased binding activity, but higher levels of G3DeltaEGF products were able to inhibit the binding of G3 to the cell surface. G3DeltaEGF expression inhibited secretion of endogenous versican in astrocytoma cells and also inhibited the secretion of mini-versican in COS-7 cells co-transfected with the mini-versican and G3DeltaEGF constructs. The effect seems to depend on the expression efficiency of G3DeltaEGF, and it occurred via the carbohydrate recognition domain. |
| Databáze: | OpenAIRE |
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