Recognition and ubiquitination of Notch by Itch, a hect-type E3 ubiquitin ligase.
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.
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA.
L
L
Qiu
C
C
Joazeiro
N
N
Fang
H Y
HY
Wang
C
C
Elly
Y
Y
Altman
D
D
Fang
T
T
Hunter
Y C
YC
Liu
D000818:Animals; D006801:Humans; D019169:Jurkat Cells; D008025:Ligases / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011537:Pruritus / Q000235:genetics; D051880:Receptors, Notch; D011993:Recombinant Fusion Proteins; D015398:Signal Transduction; D014162:Transfection; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000378:metabolism*
D008565:Membrane Proteins; D051880:Receptors, Notch; D011993:Recombinant Fusion Proteins; D014452:Ubiquitins; C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases; D008025:Ligases