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
DOIs
StatePublished - Feb 5 2001

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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    Kim, J. W., Chang, T. S., Lee, J. E., Huh, S. H., Yeon, S. W., Yang, W. S., Joe, C. O., Mook-Jung, I., Tanzi, R. E., Kim, T. W., & Choi, E. J. (2001). Negative regulation of the SAPK/JNK signaling pathway by presenilin 1. Journal of Cell Biology, 152(3), 457-463. https://doi.org/10.1083/jcb.153.3.457