Recognition and ubiquitination of Notch by Itch, a Hect-type E3 ubiquitin ligase

L. Qiu, C. Joazeiro, N. Fang, H. Y. Wang, C. Elly, Y. Altman, D. Fang, T. Hunter, Y. C. Liu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

265 Scopus citations

Abstract

Genetic studies identified Itch, which is a homologous to the E6-associated protein carboxyl terminus (Hect) domain-containing E3 ubiquitin-protein ligase that is disrupted in non-agouti lethal mice or Itchy mice. Itch-deficiency results in abnormal immune responses and constant itching in the skin. Here, Itch was shown to associate with Notch, a protein involved in cell fate decision in many mammalian cell types, including cells in the immune system. Itch binds to the N-terminal portion of the Notch intracellular domain via its WW domains and promotes ubiquitination of Notch through its Hect ubiquitin ligase domain. Thus, Itch may participate in the regulation of immune responses by modifying Notch-mediated signaling.

Original languageEnglish (US)
Pages (from-to)35734-35737
Number of pages4
JournalJournal of Biological Chemistry
Volume275
Issue number46
DOIs
StatePublished - Nov 17 2000

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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