title: Binding to syntenin-1 protein defines a new mode of ubiquitin-based interactions regulated by phosphorylation.
abstract: Syntenin-1 is a PDZ domain-containing adaptor that controls trafficking of transmembrane proteins including those associated with tetraspanin-enriched microdomains. We describe the interaction of syntenin-1 with ubiquitin through a novel binding site spanning the C terminus of ubiquitin, centered on Arg(72), Leu(73), and Arg(74). A conserved LYPSL sequence in the N terminus, as well as the C-terminal region of syntenin-1, are essential for binding to ubiquitin. We present evidence for the regulation of this interaction through syntenin-1 dimerization. We have also established that syntenin-1 is phosphorylated downstream of Ulk1, a serine/threonine kinase that plays a critical role in autophagy and regulates endocytic trafficking. Importantly, Ulk1-dependent phosphorylation of Ser(6) in the LYPSL prevents the interaction of syntenin-1 with ubiquitin. These results define an unprecedented ubiquitin-dependent pathway involving syntenin-1 that is regulated by Ulk1.
authors.affiliation: School of Cancer Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.
authors.forename: Sundaresan
authors.initials: S
authors.lastname: Rajesh
authors.forename: Ružica
authors.initials: R
authors.lastname: Bago
authors.forename: Elena
authors.initials: E
authors.lastname: Odintsova
authors.forename: Gayrat
authors.initials: G
authors.lastname: Muratov
authors.forename: Gouri
authors.initials: G
authors.lastname: Baldwin
authors.forename: Pooja
authors.initials: P
authors.lastname: Sridhar
authors.forename: Sandya
authors.initials: S
authors.lastname: Rajesh
authors.forename: Michael
authors.initials: M
authors.lastname: Overduin
authors.forename: Fedor
authors.initials: F
authors.lastname: Berditchevski
mesh_terms: D020816:Amino Acid Motifs; D001343:Autophagy / Q000502:physiology; D000071189:Autophagy-Related Protein-1 Homolog; D001665:Binding Sites; D001693:Biological Transport, Active / Q000502:physiology; D004705:Endocytosis / Q000502:physiology; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D011485:Protein Binding; D055503:Protein Multimerization / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D053676:Syntenins / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C109621:SDCBP protein, human; D053676:Syntenins; D025801:Ubiquitin; D000071189:Autophagy-Related Protein-1 Homolog; D017346:Protein Serine-Threonine Kinases; C484754:ULK1 protein, human