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Negative regulation of the SAPK/JNK signaling pathway by presenilin 1.

Kim, JW; Chang, TS; Lee, JE; Huh, SH; Yeon, SW; Yang, WS; Joe, CO; Mook-Jung, I; Tanzi, RE; Kim, TW; Choi, EJ
The Journal of cell biology, 153(3):457-463, 2001
Journal Title
The Journal of cell biology
Presenilin 1 (PS1) plays a pivotal role in Notch signaling and the intracellular metabolism of the amyloid beta-protein. To understand intracellular signaling events downstream of PS1, we investigated in this study the action of PS1 on mitogen-activated protein kinase pathways. Overexpressed PS1 suppressed the stress-induced stimulation of stress-activated protein kinase (SAPK)/c-Jun NH(2)-terminal kinase (JNK) in human embryonic kidney 293 cells. Interestingly, two functionally inactive PS1 mutants, PS1(D257A) and PS1(D385A), failed to inhibit UV-stimulated SAPK/JNK. Furthermore, H(2)O(2-) or UV-stimulated SAPK activity was higher in mouse embryonic fibroblast (MEF) cells from PS1-null mice than in MEF cells from PS(+/+) mice. MEF(PS1(-/-)) cells were more sensitive to the H(2)O(2)-induced apoptosis than MEF(PS1(+/+)) cells. Ectopic expression of PS1 in MEF(PS1(-/-)) cells suppressed H(2)O(2)-stimulated SAPK/JNK activity and apoptotic cell death. Together, our data suggest that PS1 inhibits the stress-activated signaling by suppressing the SAPK/JNK pathway.
MeSH terms
AnimalsApoptosisHumansHydrogen Peroxide/pharmacologyJNK Mitogen-Activated Protein KinasesMembrane Proteins/geneticsMembrane Proteins/metabolism*MiceMice, Mutant StrainsMitogen-Activated Protein Kinases/antagonists & inhibitorsMitogen-Activated Protein Kinases/metabolism*Neuroblastoma/metabolismPresenilin-1Recombinant Proteins/metabolismSignal TransductionUltraviolet Rays/adverse effects
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Journal Papers > Research Organization > Brain Disease Research Center
AJOU Authors
묵, 인희
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