Inhibition of PDGF-B induction and cell growth by syndecan-1 involves the ubiquitin and SUMO-1 ligase, Topors
Syndecans are receptors for soluble ligands, including heparin-binding growth factors, and matrix proteins. However, intracellular targets of syndecan-1 (Sdc-1)-mediated signaling are not fully understood. A yeast two-hybrid protein interaction screening of a mouse embryo library identified the ubiq...
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| Veröffentlicht in: | PloS one 2012-08, Vol.7 (8), p.e43701 |
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| description | Syndecans are receptors for soluble ligands, including heparin-binding growth factors, and matrix proteins. However, intracellular targets of syndecan-1 (Sdc-1)-mediated signaling are not fully understood. A yeast two-hybrid protein interaction screening of a mouse embryo library identified the ubiquitin and SUMO-1 E3 ligase, Topors, as a novel ligand of the Sdc-1 cytoplasmic domain (S1CD), a finding confirmed by ligand blotting and co-precipitation with Sdc-1 from cell lysates. Deletion mutagenesis identified an 18-amino acid sequence of Topors required for the interaction with the S1CD. By immunohistochemistry, Topors and Sdc-1 co-localized near the cell periphery in normal murine mammary gland (NMuMG) cells in vitro and in mouse embryonic epithelia in vivo. Finally, siRNA-mediated knockdown of Topors demonstrated that Topors is a growth promoter for murine arterial smooth muscle cells and is required for the inhibitory effect of Sdc-1 on cell growth and platelet-derived growth factor-B induction. These data suggest a novel mechanism for the inhibitory effects of Sdc-1 on cell growth that involves the interaction between the cytoplasmic domain of Sdc-1 and the SUMO-1 E3 ligase, Topors. |
| doi_str_mv | 10.1371/journal.pone.0043701 |
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However, intracellular targets of syndecan-1 (Sdc-1)-mediated signaling are not fully understood. A yeast two-hybrid protein interaction screening of a mouse embryo library identified the ubiquitin and SUMO-1 E3 ligase, Topors, as a novel ligand of the Sdc-1 cytoplasmic domain (S1CD), a finding confirmed by ligand blotting and co-precipitation with Sdc-1 from cell lysates. Deletion mutagenesis identified an 18-amino acid sequence of Topors required for the interaction with the S1CD. By immunohistochemistry, Topors and Sdc-1 co-localized near the cell periphery in normal murine mammary gland (NMuMG) cells in vitro and in mouse embryonic epithelia in vivo. Finally, siRNA-mediated knockdown of Topors demonstrated that Topors is a growth promoter for murine arterial smooth muscle cells and is required for the inhibitory effect of Sdc-1 on cell growth and platelet-derived growth factor-B induction. These data suggest a novel mechanism for the inhibitory effects of Sdc-1 on cell growth that involves the interaction between the cytoplasmic domain of Sdc-1 and the SUMO-1 E3 ligase, Topors.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22912899</pmid><doi>10.1371/journal.pone.0043701</doi><tpages>e43701</tpages><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1326252349 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adapter proteins Amino acid sequence Amino acids Animals Anticoagulants Binding Sites - genetics Biology Blotting, Western Cell adhesion & migration Cell Line Cell Proliferation Cells, Cultured Clonal deletion Cloning Embryos Growth Growth factors Heparan sulfate Heparin Immunohistochemistry Immunoprecipitation Intracellular signalling Kinases Ligands Ligases Localization Lymphocytes B Lysates Mammals Mammary gland Medical research Medical screening Medicine Mice Mice, Inbred C57BL Mice, Knockout Muscles Mutagenesis Mutation Myocytes, Smooth Muscle - drug effects Myocytes, Smooth Muscle - metabolism NIH 3T3 Cells Plasmids Platelet-derived growth factor Precipitation (Meteorology) Protein Binding Proteins Proto-Oncogene Proteins c-sis - genetics Proto-Oncogene Proteins c-sis - metabolism Receptors RNA Interference Rodents Signal transduction siRNA Smooth muscle Studies Sumo Surgery Syndecan Syndecan-1 - genetics Syndecan-1 - metabolism Thrombin - pharmacology Two-Hybrid System Techniques Ubiquitin Ubiquitin-protein ligase Ubiquitin-Protein Ligases - genetics Ubiquitin-Protein Ligases - metabolism Yeast |
| title | Inhibition of PDGF-B induction and cell growth by syndecan-1 involves the ubiquitin and SUMO-1 ligase, Topors |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-21T21%3A49%3A20IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Inhibition%20of%20PDGF-B%20induction%20and%20cell%20growth%20by%20syndecan-1%20involves%20the%20ubiquitin%20and%20SUMO-1%20ligase,%20Topors&rft.jtitle=PloS%20one&rft.au=Braun,%20Kathleen%20R&rft.date=2012-08-17&rft.volume=7&rft.issue=8&rft.spage=e43701&rft.pages=e43701-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0043701&rft_dat=%3Cgale_plos_%3EA498260249%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1326252349&rft_id=info:pmid/22912899&rft_galeid=A498260249&rft_doaj_id=oai_doaj_org_article_d1067a71f8b64f15a4ce28c9d9b731bf&rfr_iscdi=true |