c-Jun controls the efficiency of MAP kinase signaling by transcriptional repression of MAP kinase phosphatases

Amy Sprowles, Dan Robinson, Yi Mi Wu, Hsing Jien Kung, Ron Wisdom

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The mammalian JNK signaling pathway regulates the transcriptional response of cells to environmental stress, including UV irradiation. This signaling pathway is composed of a classical MAP kinase cascade; activation results in phosphorylation of the transcription factor substrates c-Jun and ATF2, and leads to changes in gene expression. The defining components of this pathway are conserved in the fission yeast S. pombe, where the genetic studies have shown that the ability of the JNK homolog Spc1 to be activated in response to UV irradiation is dependent on the presence of the transcription factor substrate Atf1. We have used genetic analysis to define the role of c-Jun in activation of the mammalian JNK signaling pathway. Our results show that optimal activation of JNK requires the presence of its transcription factor substrate c-Jun. Mutational analysis shows that the ability of c-Jun to support efficient activation of JNK requires the ability of Jun to bind DNA, suggesting a transcriptional mechanism. Consistent with this, we show that c-Jun represses the expression of several MAP kinase phosphatases. In the absence of c-Jun, the increased expression of MAP kinase phosphatases leads to impaired activation of the ERK, JNK, and p38 MAP kinases after pathway activation. The results show that one function of c-Jun is to regulate the efficiency of signaling by the ERK, p38, and JNK MAP kinases, a function that is likely to affect cellular responses to many different stimuli.

Original languageEnglish
Pages (from-to)459-468
Number of pages10
JournalExperimental Cell Research
Volume308
Issue number2
DOIs
Publication statusPublished - Aug 15 2005
Externally publishedYes

Keywords

  • c-Jun
  • MAP kinase phosphatase
  • S. pombe

ASJC Scopus subject areas

  • Cell Biology

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