Notch interferes with the scaffold function of JNK-interacting protein 1 to inhibit the JNK signaling pathway.
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.
Kim
Jin Woo
JW
National Creative Research Initiative Center for Cell Death, School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea.
Kim
Myung Jin
MJ
Kim
Kwang Je
KJ
Yun
Hee Jae
HJ
Chae
Ji Soo
JS
Hwang
Sang Gil
SG
Chang
Tong-Shin
TS
Park
Hee-Sae
HS
Lee
Kang-Woo
KW
Han
Pyung-Lim
PL
Cho
Ssang-Goo
SG
Kim
Tae-Wan
TW
Choi
Eui-Ju
EJ
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*
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