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

Jin Woo Kim, Tong Shin Chang, Ji Eun Lee, Sung Ho Huh, Seung Woo Yeon, Wan Seok Yang, Cheol O. Joe, Inhee Mook-Jung, Rudolph E. Tanzi, Tae Wan Kim, Eui Ju Choi

    Research output: Contribution to journalArticlepeer-review

    28 Citations (Scopus)

    Abstract

    Presenilin 1 (PS1) plays a pivotal role in Notch signaling and the intracellular metabolism of the amyloid β-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 NH2-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, H2O2- or UV-stimulated SAPK activity was higher in mouse embryonic fibroblast (MEF) cells from PS1-null mice than in MEF cells from PS+/+ mice. MEFPS1(-/-) cells were more sensitive to the H2O2-induced apoptosis than MEFPS1(+/+) cells. Ectopic expression of PS1 in MEFPS1(-/-) cells suppressed H2O2-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.

    Original languageEnglish
    Pages (from-to)457-463
    Number of pages7
    JournalJournal of Cell Biology
    Volume152
    Issue number3
    DOIs
    Publication statusPublished - 2001 Feb 5

    Keywords

    • Apoptosis
    • Presenilin 1
    • Stress-activated protein kinase
    • c-Jun NH-terminal kinase
    • γ-secretase

    ASJC Scopus subject areas

    • Cell Biology

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