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

doi:10.1083/jcb.153.3.457

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

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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. MEF^PS1(-/-) cells were more sensitive to the H₂O₂-induced apoptosis than MEF^PS1(+/+) cells. Ectopic expression of PS1 in MEF^PS1(-/-) 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 language	English
Pages (from-to)	457-463
Number of pages	7
Journal	Journal of Cell Biology
Volume	152
Issue number	3
DOIs	https://doi.org/10.1083/jcb.153.3.457
Publication status	Published - 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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title = "Negative regulation of the SAPK/JNK signaling pathway by presenilin 1",

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.",

keywords = "Apoptosis, Presenilin 1, Stress-activated protein kinase, c-Jun NH-terminal kinase, γ-secretase",

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

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AU - Kim, Jin Woo

AU - Chang, Tong Shin

AU - Lee, Ji Eun

AU - Huh, Sung Ho

AU - Yeon, Seung Woo

AU - Yang, Wan Seok

AU - Joe, Cheol O.

AU - Mook-Jung, Inhee

AU - Tanzi, Rudolph E.

AU - Kim, Tae Wan

AU - Choi, Eui Ju

PY - 2001/2/5

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AB - 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.

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

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