Binding to syntenin-1 defines a new mode of ubiquitin-based interactions regulated by phosphorylation.
Research output: Contribution to journal › Article
Authors
Colleges, School and Institutes
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 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.
Details
Original language | English |
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Pages (from-to) | 39606-39614 |
Journal | Journal of Biological Chemistry |
Volume | 286 |
Publication status | Published - 26 Sep 2011 |