Molecular mechanisms of coupled monoubiquitination

Tanja Woelk, Barbara Oldrini, Elena Maspero, Stefano Confalonieri, Elena Cavallaro, Pier Paolo Di Fiore, Simona Polo

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Abstract

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.

Original languageEnglish
Pages (from-to)1246-1254
Number of pages9
JournalNature Cell Biology
Volume8
Issue number11
DOIs
Publication statusPublished - Nov 2006

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ASJC Scopus subject areas

  • Cell Biology

Cite this

Woelk, T., Oldrini, B., Maspero, E., Confalonieri, S., Cavallaro, E., Di Fiore, P. P., & Polo, S. (2006). Molecular mechanisms of coupled monoubiquitination. Nature Cell Biology, 8(11), 1246-1254. https://doi.org/10.1038/ncb1484