title: Notch interferes with the scaffold function of JNK-interacting protein 1 to inhibit the JNK signaling pathway.
abstract: The transmembrane protein Notch is cleaved by gamma-secretase to yield an active form, Notch intracellular domain (Notch-IC), in response to the binding of ligands, such as Jagged. Notch-IC contributes to the regulation of a variety of cellular events, including cell fate determination during embryonic development as well as cell growth, differentiation, and survival. We now show that Notch1-IC suppresses the scaffold activity of c-Jun N-terminal kinase (JNK)-interacting protein 1 (JIP1) in the JNK signaling pathway. Notch1-IC physically associated with the JNK binding domain of JIP1 and thereby interfered with the interaction between JIP1 and JNK. JIP1 mediated the activation of JNK1 induced by glucose deprivation in mouse embryonic fibroblasts, and ectopic expression of Notch1-IC inhibited JNK activation and apoptosis triggered by glucose deprivation. Taken together, these findings suggest that Notch1-IC negatively regulates the JNK pathway by disrupting the scaffold function of JIP1.
authors.affiliation: National Creative Research Initiative Center for Cell Death, School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea.
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Kim
authors.forename: Myung Jin
authors.initials: MJ
authors.lastname: Kim
authors.forename: Kwang Je
authors.initials: KJ
authors.lastname: Kim
authors.forename: Hee Jae
authors.initials: HJ
authors.lastname: Yun
authors.forename: Ji Soo
authors.initials: JS
authors.lastname: Chae
authors.forename: Sang Gil
authors.initials: SG
authors.lastname: Hwang
authors.forename: Tong-Shin
authors.initials: TS
authors.lastname: Chang
authors.forename: Hee-Sae
authors.initials: HS
authors.lastname: Park
authors.forename: Kang-Woo
authors.initials: KW
authors.lastname: Lee
authors.forename: Pyung-Lim
authors.initials: PL
authors.lastname: Han
authors.forename: Ssang-Goo
authors.initials: SG
authors.lastname: Cho
authors.forename: Tae-Wan
authors.initials: TW
authors.lastname: Kim
authors.forename: Eui-Ju
authors.initials: EJ
authors.lastname: Choi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002460:Cell Line; D005822:Genetic Vectors / Q000235:genetics; D005947:Glucose / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D036341:Intercellular Signaling Peptides and Proteins; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D000072100:Jagged-1 Protein; D008156:Luciferases; D008565:Membrane Proteins / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; C490666:MAPK8IP1 protein, human; D008565:Membrane Proteins; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D000072099:Serrate-Jagged Proteins; D008156:Luciferases; D048031:JNK Mitogen-Activated Protein Kinases; D005947:Glucose