Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 275, Issue 46, Pages 35734-35737Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M007300200
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- NIDDK NIH HHS [DK56558] Funding Source: Medline
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Genetic studies identified Itch, which is a homologous to the EG-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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