Itch: A HECT-type E3 ligase regulating immunity, skin and cancer

G. Melino, E. Gallagher, R. I. Aqeilan, R. Knight, A. Peschiaroli, M. Rossi, F. Scialpi, M. Malatesta, L. Zocchi, G. Browne, A. Ciechanover, F. Bernassola*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

146 Scopus citations


The HECT-type E3 ubiquitin ligase (E3) Itch is absent in the non-agouti-lethal 18H or Itchy mice, which develop a severe immunological disease, including lung and stomach inflammation and hyperplasia of lymphoid and hematopoietic cells. The involvement of Itch in multiple signaling pathways and pathological conditions is presently an area of extensive scientific interest. This review aims to bring together a growing body of work exploring Itch-regulated biological processes, and to highlight recent discoveries on the regulatory mechanisms modulating its catalytic activity and substrate recognition capability. Our contribution is also an endeavor to correlate Itch substrate specificity with the pathological defects manifested by the mutant Itchy mice.

Original languageAmerican English
Pages (from-to)1103-1112
Number of pages10
JournalCell Death and Differentiation
Issue number7
StatePublished - Jul 2008
Externally publishedYes

Bibliographical note

Funding Information:
Acknowledgements. We sincerely apologize for not being able to cite some relevant references because of space constraints. This work has been supported by EU-Grant EPISTEM LSHB-CT-019067; the AIRC Grant 1338; the ISS Grant no. 530/F-A19, Grant Telethon GGPO4110, and Philip Morris grant awarded to GM, and by the EU NeOEs Rubicon and NeuroNE, the Israel Science Foundation, the German Israeli Foundation, the Israel Cancer Research Fund, and the Dr. Miriam and Sheldon Adelson Medical Research Foundation awarded to AC.


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