Notchless encodes a novel WD40-repeat-containing protein that modulates Notch signaling activity.
Signaling by Notch family receptors is involved in many cell-fate decisions during development. Several modifiers of Notch activity have been identified, suggesting that regulation of Notch signaling is complex. In a genetic screen for modifiers of Notch activity, we identified a gene encoding a novel WD40-repeat protein. The gene is called Notchless, because loss-of-function mutant alleles dominantly suppress the wing notching caused by certain Notch alleles. Reducing Notchless activity increases Notch activity. Overexpression of Notchless in Xenopus or Drosophila appears to have a dominant-negative effect in that it also increases Notch activity. Biochemical studies show that Notchless binds to the cytoplasmic domain of Notch, suggesting that it serves as a direct regulator of Notch signaling activity.
Royet
J
J
European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Bouwmeester
T
T
Cohen
S M
SM
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins; D017344:Genes, Insect; D006257:Head / Q000033:anatomy & histology; D019476:Insect Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D051880:Receptors, Notch; D020449:Repetitive Sequences, Amino Acid; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013489:Suppression, Genetic; D013909:Thorax / Q000033:anatomy & histology; D014921:Wings, Animal / Q000033:anatomy & histology; D014981:Xenopus / Q000235:genetics*
C086679:DX protein, Drosophila; D029721:Drosophila Proteins; D019476:Insect Proteins; D008565:Membrane Proteins; C497759:N protein, Drosophila; C117007:Nle protein, Drosophila; D051880:Receptors, Notch