Article abstract
Nature Cell Biology 8, 1246 - 1254 (2006)
Published online: 1 October 2006 | doi:10.1038/ncb1484
Molecular mechanisms of coupled monoubiquitination
Tanja Woelk1, Barbara Oldrini1,4, Elena Maspero1,4, Stefano Confalonieri1, Elena Cavallaro1, Pier Paolo Di Fiore1,2,3 & Simona Polo1,2
Many proteins contain ubiquitin-binding domains or motifs (UBDs), such as the UIM (ubiquitin-interacting motif) and are referred to as ubiquitin receptors. Ubiquitin receptors themselves are frequently monoubiquitinated by a process that requires the presence of a UBD and is referred to as coupled monoubiquitination. Using a UIM-containing protein, eps15, as a model, we show here that coupled monoubiquitination strictly depends on the ability of the UIM to bind to monoubiquitin (mUb). We found that the underlying molecular mechanism is based on interaction between the UIM and a ubiquitin ligase (E3), which has itself been modified by ubiquitination. Furthermore, we demonstrate that the in vivo ubiquitination of members of the Nedd4 family of E3 ligases correlates with their ability to monoubiquitinate eps15. Thus, our results clarify the mechanism of coupled monoubiquitination and identify the ubiquitination of E3 ligases as a critical determinant in this process.
- IFOM, The FIRC Institute for Molecular Oncology, Via Adamello 16, 20139, Milan, Italy.
- European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.
- University of Milan, 20122, Milan, Italy.
- These authors contributed equally to this work.
Correspondence to: Pier Paolo Di Fiore1,2,3 e-mail: simona.polo@ifom-ieo-campus.it
Correspondence to: Simona Polo1,2 e-mail: pierpaolo.difiore@ifom-ieo-campus.it
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