1. Academic Validation
  2. Itch self-polyubiquitylation occurs through lysine-63 linkages

Itch self-polyubiquitylation occurs through lysine-63 linkages

  • Biochem Pharmacol. 2008 Dec 1;76(11):1515-21. doi: 10.1016/j.bcp.2008.07.028.
Flavia Scialpi 1 Martina Malatesta Angelo Peschiaroli Mario Rossi Gerry Melino Francesca Bernassola
Affiliations

Affiliation

  • 1 IDI-IRCCS Biochemistry Laboratory, Department of Experimental Medicine and Biochemical Sciences, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy.
Abstract

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.

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