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)


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
Issue number3
Publication statusPublished - 2001 Feb 5


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

ASJC Scopus subject areas

  • Cell Biology


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