title: MDA-9/syntenin interacts with ubiquitin via a novel ubiquitin-binding motif.
abstract: Ubiquitination appears to be involved in proteasome-dependent proteolysis and in the membrane trafficking system including endocytosis and exocytosis. In this study, we identified MDA-9/syntenin as a novel ubiquitin-binding protein by a yeast two-hybrid system using modified ubiquitin in which lysine 48 is substituted by arginine. It has been reported that MDA-9/syntenin is a membrane-associated protein and regulates a cellular process involving endocytosis and intracellular transport. We found that MDA-9/syntenin binds to ubiquitin by a non-covalent bond and is ubiquitinated covalently. MDA-9/syntenin has no ubiquitin-binding motifs that have so far been reported, suggesting that MDA-9/syntenin physically interacts with ubiquitin via a novel binding motif. MDA-9/syntenin is stable in the cell, suggesting that ubiquitin binding of MDA-9/syntenin or ubiquitination of MDA-9/syntenin is not related to proteolysis. Furthermore, we showed that overexpression of wild-type MDA-9/syntenin enhances formation of filopodia, whereas MDA-9/syntenin lacking the PDZ domain inhibits the formation of filopodia, suggesting that MDA-9/syntenin plays an important role via interaction with ubiquitin in the regulation of cancer metastasis and invasion.
authors.affiliation: Department of Biochemistry, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Okumura
authors.forename: Koichi
authors.initials: K
authors.lastname: Yoshida
authors.forename: Fei
authors.initials: F
authors.lastname: Liang
authors.forename: Shigetsugu
authors.initials: S
authors.lastname: Hatakeyama
mesh_terms: D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D003001:Cloning, Molecular; D006801:Humans; D011485:Protein Binding; D053676:Syntenins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D025801:Ubiquitin / Q000737:chemistry / Q000378:metabolism*
chemical_list: C109621:SDCBP protein, human; D053676:Syntenins; D025801:Ubiquitin