Role of suppressor of hairless in the delta-activated Notch signaling pathway.
The Notch protein (N) acts as a transmembrane receptor for intercellular signals controlling cell fate choices in vertebrates and invertebrates. Genetical and molecular evidence indicates that, during Drosophila neurogenesis, an evolutionarily conserved transcription factor, Suppressor of Hairless [Su(H)], transduces the signal of N activation by its ligand Delta (D1). Su(H) plays a direct role in the immediate response of the genome to N signaling by up-regulating the transcription of the Enhancer of split Complex [E(spl)-C] genes. These findings suggest that the N transduction pathway can be described as a simple, linear cascade of molecular activation. At the molecular level, the mechanism of Su(H) "activation" is yet unknown. Two non-exclusive models have been proposed. In the first one, Su(H) binds to inactive N at the membrane. The binding of D1 to N in the extracellular space somehow interferes with the N-mediated cytoplasmic retention of Su(H), resulting in the nuclear translocation and "activation" of Su(H). In the second model, DNA-bound Su(H) is proposed to be "activated" in the nucleus by the direct binding of a processed form of N, acting as a transcriptional coactivator. This nuclear N protein would be generated by the ligand-induced proteolytic cleavage of the N transmembrane receptor.
Lecourtois
M
M
Institut Jacques Monod, CNRS--Université Paris 7-Denis Diderot, France.
Schweisguth
F
F
D000818:Animals; D004330:Drosophila / Q000502:physiology; D029721:Drosophila Proteins; D019476:Insect Proteins / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology; D051880:Receptors, Notch; D012097:Repressor Proteins / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D029721:Drosophila Proteins; D019476:Insect Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C497759:N protein, Drosophila; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D012097:Repressor Proteins; C088731:Su(H) protein, Drosophila; C064045:delta protein