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

Cell Signal. 2002 Jul;14(7):585-93. doi: 10.1016/s0898-6568(01)00275-3.

Abstract

The regulation of c-Jun transcriptional activity by Jun N-terminal kinase (JNK) has become a paradigm for understanding how mitogen-activated protein (MAP) kinase signalling pathways elicit specific changes in gene transcription through selective phosphorylation of nuclear transcription factors. Selective phosphorylation of c-Jun by JNK is determined by a specific docking motif in c-Jun, the delta region, which enables JNK to associate physically with c-Jun. Analogous MAP kinase docking motifs have subsequently been found in several other transcription factors, indicating that this is a general mechanism for ensuring specificity of signal transduction. Genetic and biochemical studies in mice, flies and cultured cells have provided evidence that signals relayed by JNK through c-Jun regulate a range of cellular processes including cell proliferation, tumourigenesis, apoptosis and embryonic development. Despite these advances, in most cases, the genes or programs of gene expression downstream of JNK and c-Jun, which control these processes, have not been defined. Here, we review the current understanding of the molecular basis and biological consequences of JNK signalling via c-Jun and highlight some of the mechanistic issues, which remain to be resolved.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis
  • Cell Division
  • JNK Mitogen-Activated Protein Kinases
  • MAP Kinase Signaling System*
  • Mitogen-Activated Protein Kinases / metabolism*
  • Mitogen-Activated Protein Kinases / physiology*
  • Morphogenesis
  • Neoplasms / etiology
  • Phosphorylation
  • Proto-Oncogene Proteins c-jun / metabolism*
  • Transcriptional Activation

Substances

  • Proto-Oncogene Proteins c-jun
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases