Keeping JNK in its place
The nucleus, housing the genomic information store of DNA in the protein-complexed form called chromatin, is of central importance in the compartmentalised eukaryotic cell. c-Jun N-terminal Kinase (JNK) signalling plays key roles in the signalling events activated by stress and during fundamental processes of development. Our recent studies analysing JNK1 nuclear trafficking challenge the paradigm of uni-directional signalling: live imaging reveals continued nucleus-cytoplasmic shuttling of JNK1 with its major determinant for nuclear entry mapped to its C-terminal sequence and not correlated with its activation. Furthermore, unanticipated links between JNK and the Nuclear Factor-Y (NF-Y) transcription factor may provide additional levels of control, whereby chromatin-associated acetylases modify JNK in an unappreciated regulatory platform for sending nucleus-initiated signals back to the cytoplasm, i.e. nucleo-radiant signaling, representing a novel mechanism that integrates nuclear actions by creating a signal transduction circuit triggered by environmental or genetic factors. These observations underpin a series of projects that aim to define the critical features of JNK that dictate its nuclear trafficking, to explore the impact of JNK post-translational modifications on its trafficking and kinase activity and to define JNK’s contribution to the NF-Y regulatory platform and nucleo-radiant signalling. Key methodologies used in these projects will include high resolution and live imaging, together with fundamental biochemical approaches to the creation and deployment of novel recombinant forms of modified JNKs.
Professor David Jans, Monash University
Professor Attila Remenyl, Hungary
Professor Roberto Mantovani, Italy
ARC Discovery Grant 2016-22018
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- Misheva M, Kaur G, Ngoei KR, Yeap YY, Ng IH, Wagstaff KM, Ng DC, Jans DA, Bogoyevitch MA. Intracellular mobility and nuclear trafficking of the stress-activated kinase JNK1 are impeded by hyperosmotic stress. Biochim Biophys Acta 2014 ;1843(2): 253-64.
- Zeke A, Misheva M, Remenyi A, Bogoyevitch MA. JNK signaling: regulation and functions based on complex protein-protein partnerships Mol Microbiol Reviews 2016 in press.
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