Binding to syntenin-1 defines a new mode of ubiquitin-based interactions regulated by phosphorylation.

Sundaresan Rajesh, Ruzica Bago, Elena Odintsova, G Muratov, Gouri Baldwin, Pooja Sridhar, Sandya Rajesh, Michael Overduin, Fedor Berditchevski

Research output: Contribution to journalArticle

28 Citations (Scopus)


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 Arg72, Leu73 and Arg74 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 down-stream of Ulk1, a serine-threonine kinase that plays a critical role in autophagy and regulates endocytic trafficking. Importantly, Ulk1-dependent phosphorylation of Ser6 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.
Original languageEnglish
Pages (from-to)39606-39614
JournalJournal of Biological Chemistry
Publication statusPublished - 26 Sept 2011


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