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

Authors
  • Qiu, L
  • Joazeiro, C
  • Fang, N
  • Wang, H Y
  • Elly, C
  • Altman, Y
  • Fang, D
  • Hunter, T
  • Liu, Y C
Type
Published Article
Journal
Journal of Biological Chemistry
Publisher
American Society for Biochemistry & Molecular Biology (ASBMB)
Publication Date
Nov 17, 2000
Volume
275
Issue
46
Pages
35734–35737
Identifiers
PMID: 10940313
Source
Medline
License
Unknown

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.

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