Itch self-polyubiquitylation occurs through lysine-63 linkages

Flavia Scialpi, Martina Malatesta, Angelo Peschiaroli, Mario Rossi, Gerry Melino, Francesca Bernassola

Research output: Contribution to journalArticle


Itch, an E3 protein ubiquitin ligase (E3), which belongs to the homologous to E6-AP carboxy terminus (HECT)-type subfamily, catalyzes its own ubiquitylation. The precise nature of Itch-mediated self-modification and its biological outcome are not completely understood. Here, we show that Itch auto-ubiquitylation is an intermolecular reaction generating Lys63-linkages, rather than the Lys48-linked polyubiquitin chains that target proteins for proteasomal degradation. As a result, Itch is a relatively high stable protein, whose levels are not significantly affected by treatment by either proteasome or lysosome inhibitors. Furthermore, we demonstrate that the decay rate of a catalytic inactive Itch mutant, which is devoided of self-ubiquitylating activity, is barely indistinguishable from the one of the wild-type protein. These data definitely establish a nondegradative role for Lys63-linked Itch self-ubiquitylation.

Original languageEnglish
Pages (from-to)1515-1521
Number of pages7
JournalBiochemical Pharmacology
Issue number11
Publication statusPublished - Dec 1 2008



  • E3 ubiquitin ligases
  • HECT domain
  • Protein ubiquitylation

ASJC Scopus subject areas

  • Pharmacology
  • Biochemistry

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