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Molecular mechanism and biological functions of c-Jun N-terminal kinase signalling via the c-Jun transcription factor

Catherine Dunn1, Carolyn Wiltshire, Ann MacLaren

  • 1Institute of Biomedical and Life Sciences, University of Glasgow, G12 8QQ, Glasgow, UK.

Cellular Signalling
|April 17, 2002
PubMed

Insights

Jun N-terminal kinase (JNK) regulates c-Jun activity through a specific docking motif, impacting cell proliferation, apoptosis, and development. The downstream genes controlled by this pathway remain largely undefined.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Genetics

Background:

  • Mitogen-activated protein (MAP) kinase pathways, like Jun N-terminal kinase (JNK), regulate gene transcription via phosphorylation of transcription factors.
  • The c-Jun transcription factor's activity is modulated by JNK, serving as a model for signal transduction specificity.

Purpose of the Study:

  • To review the molecular mechanisms and biological outcomes of JNK signaling through c-Jun.
  • To highlight unresolved questions regarding the downstream gene targets and regulatory programs controlled by JNK-c-Jun signaling.

Main Methods:

  • Review of genetic and biochemical studies in mice, flies, and cell cultures.
  • Analysis of literature on MAP kinase docking motifs and transcription factor regulation.

Main Results:

  • JNK selectively phosphorylates c-Jun via a delta region docking motif, ensuring signal specificity.
  • This pathway regulates critical cellular processes including proliferation, tumorigenesis, apoptosis, and embryonic development.
  • Analogous docking motifs are found in other transcription factors, indicating a general mechanism for signal transduction specificity.

Conclusions:

  • JNK-mediated regulation of c-Jun is a key signaling mechanism with broad biological implications.
  • Defining the specific genes and gene expression programs downstream of JNK-c-Jun is crucial for understanding its role in cellular processes.
  • Further research is needed to resolve mechanistic aspects of this signaling pathway.

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