Molecular mechanism and biological functions of c-Jun N-terminal kinase signalling via the c-Jun transcription factor.
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.
Dunn
Catherine
C
Institute of Biomedical and Life Sciences, University of Glasgow, G12 8QQ, Glasgow, UK.
Wiltshire
Carolyn
C
MacLaren
Ann
A
Gillespie
David A F
DA
D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D048031:JNK Mitogen-Activated Protein Kinases; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism* / Q000502:physiology*; D009024:Morphogenesis; D009369:Neoplasms / Q000209:etiology; D010766:Phosphorylation; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D015533:Transcriptional Activation
D016755:Proto-Oncogene Proteins c-jun; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases