Selenite inhibits the c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) through a thiol redox mechanism

Hee Sae Park, Eun Park, Mi Sung Kim, Kwangseog Ahn, Ick Young Kim, Eui Ju Choi

Research output: Contribution to journalArticle

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Abstract

Selenium, an essential biological trace element, has been shown to modulate functions of many regulatory proteins involved in signal transduction and to affect a variety of cellular activities including cell growth, survival, and death. The molecular mechanism by which selenium exerts its action on the cellular events, however, remains unclear. In our present study, we observed that selenite suppresses both the c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) and the p38 mitogen- activated protein kinase pathway in 293T cells. In contrast, selenite had little effect on the extracellular signal-regulated kinase pathway. Furthermore, selenite directly inhibited JNK/SAPK activity in vitro but not the p38 activity. The in vitro inhibition of JNK/SAPK by selenite was reversed by the addition of reducing agents such as dithiothreitol and β- mercapto-ethanol. Replacement of cysteine 116 in JNK1 by serine abolished the inhibitory effect of selenite on JNK1 activity both in vitro and in vivo. Selenite also suppressed a c-Jun-dependent luciferase reporter activity stimulated through the JNK signaling pathway. Taken together, our findings strongly suggest that selenite differentially modulates the mammalian mitogen-activated protein kinase pathways and that it can repress the JNK/SAPK signaling pathway by inhibiting JNK/SAPK through a thiol redox mechanism.

Original languageEnglish
Pages (from-to)2527-2531
Number of pages5
JournalJournal of Biological Chemistry
Volume275
Issue number4
DOIs
Publication statusPublished - 2000 Jan 28

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Selenious Acid
JNK Mitogen-Activated Protein Kinases
Heat-Shock Proteins
Sulfhydryl Compounds
Protein Kinases
Oxidation-Reduction
Selenium
Signal transduction
MAP Kinase Signaling System
HEK293 Cells
Dithiothreitol
Reducing Agents
Extracellular Signal-Regulated MAP Kinases
Trace Elements
Cell growth
p38 Mitogen-Activated Protein Kinases
Cell death
Mitogen-Activated Protein Kinases
Luciferases
Serine

ASJC Scopus subject areas

  • Biochemistry

Cite this

Selenite inhibits the c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) through a thiol redox mechanism. / Park, Hee Sae; Park, Eun; Kim, Mi Sung; Ahn, Kwangseog; Kim, Ick Young; Choi, Eui Ju.

In: Journal of Biological Chemistry, Vol. 275, No. 4, 28.01.2000, p. 2527-2531.

Research output: Contribution to journalArticle

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