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 journalArticle

27 Scopus citations

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

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Keywords

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

ASJC Scopus subject areas

  • Cell Biology

Cite this

Kim, J. W., Chang, T. S., Lee, J. E., Huh, S. H., Yeon, S. W., Yang, W. S., ... Choi, E. J. (2001). Negative regulation of the SAPK/JNK signaling pathway by presenilin 1. Journal of Cell Biology, 152(3), 457-463.