Review articleMolecular mechanism and biological functions of c-Jun N-terminal kinase signalling via the c-Jun transcription factor
Section snippets
The c-Jun activation domain (AD) is selectively phosphorylated and stimulated by Jun N-terminal kinase (JNK)
c-Jun was originally identified as the normal cellular counterpart of the viral Jun oncoprotein (v-Jun) encoded by an avian sarcoma virus (ASV17) [1]. The 39-kDa c-Jun protein consists of a C-terminal basic region-leucine zipper (B-ZIP) DNA binding domain and a N-terminal transcriptional activation domain. c-Jun is the prototype of a large group of B-ZIP proteins, which form homo- and heterodimeric complexes capable of binding TPA response element (TRE) DNA recognition motifs (consensus
Biological functions of JNK signalling to c-Jun
As with other MAP kinase cascades, the JNK pathway is thought to regulate many different aspects of cell behaviour. However, in most cases, it remains unclear whether the critical downstream JNK substrate or substrates in any given situation includes c-Jun or indeed whether changes in gene transcription play a major role in determining the biological response. The present discussion therefore will briefly outline three examples where biochemical or genetic data implicate c-Jun as a specific and
Conclusions and future perspectives
Recent years have seen remarkable advances in our understanding of how JNK MAP kinases regulate c-Jun transcriptional activity and an emerging appreciation that signals transmitted through this mechanism control a number of fundamental cellular processes. Many of these processes, such as cell proliferation and survival, are relevant to human malignant or degenerative disease, and there is little doubt that this understanding will lead to manipulation of JNK/c-Jun signal transduction for
Acknowledgements
The authors are grateful to the Cancer Research Campaign of the United Kingdom (CRC) and to the Association for International Cancer Research (AICR) for support and to J.A. Wyke for comments on the manuscript.
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