Functional diversity among Notch1, Notch2, and Notch3 receptors.
To clarify functional diversities among the Notch receptors, we generated truncated forms of Notch1, Notch2, and Notch3 comprising the intracellular domain (aN1, aN2, and aN3) and investigated their transcriptional activities for HES1 and HES5 promoters driving the luciferase reporter gene (HES1-Luc and HES5-Luc). The reporter assays demonstrated that the transcriptional activities of aNs were markedly different from each other and dependent on the promoters examined. Furthermore, relative activities between some aN and another for each promoter were altered by the expression level of RBP-J kappa. We also found that the activities of aN1 and aN3 were reduced by coexpression of aN2. These observations suggest that each Notch receptor has a diverse role in the downstream gene expression and that the levels of HES1 and HES5 gene expression are complexly determined by various factors, such as the type and combination of the Notch receptors which confer the downstream signals and the expression level of RBP-J kappa.
Shimizu
Kiyoshi
K
Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Chiba
Shigeru
S
Saito
Toshiki
T
Kumano
Keiki
K
Hamada
Yoshio
Y
Hirai
Hisamaru
H
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D016466:CHO Cells; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D017930:Genes, Reporter; D018398:Homeodomain Proteins / Q000235:genetics; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D051379:Mice; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D051881:Receptor, Notch1; D051883:Receptor, Notch2; D000071656:Receptor, Notch3; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D051880:Receptors, Notch; D012097:Repressor Proteins / Q000235:genetics; D015398:Signal Transduction; D000072056:Transcription Factor HES-1; D014157:Transcription Factors; D015533:Transcriptional Activation; D014162:Transfection
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D008565:Membrane Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D051881:Receptor, Notch1; D051883:Receptor, Notch2; D000071656:Receptor, Notch3; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D012097:Repressor Proteins; D000072056:Transcription Factor HES-1; D014157:Transcription Factors; C489734:Hes1 protein, mouse; C489685:Hes5 protein, mouse; C497762:Notch1 protein, mouse; C497765:Notch2 protein, mouse; C499373:Notch3 protein, mouse; C497571:Rbpj protein, mouse; C073572:Notch4 protein, mouse; C077478:HES5 protein, human