Inhibition of PDGF-B induction and cell growth by syndecan-1 involves the ubiquitin and SUMO-1 ligase, Topors.

Autor: Kathleen R Braun, Allison M DeWispelaere, Steven L Bressler, Nozomi Fukai, Richard D Kenagy, Lihua Chen, Alexander W Clowes, Michael G Kinsella
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Zdroj: PLoS ONE, Vol 7, Iss 8, p e43701 (2012)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0043701
Popis: 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.
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