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Signalling to the Epigenome: New Insights into the roles of nuclear signalling kinases in the context of the immune system and cancer

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Signal Transduction Kinases are highly conserved and tightly regulated in order to initiate specific transcriptional programs in response to different external cues. While the action of signalling kinases was thought to occur predominantly in the cytoplasm, recent emerging studies have been shown they ...

Signal Transduction Kinases are highly conserved and tightly regulated in order to initiate specific transcriptional programs in response to different external cues. While the action of signalling kinases was thought to occur predominantly in the cytoplasm, recent emerging studies have been shown they regulate gene expression by translocating to the nucleus, and stably associating with the promoter and transcribed regions of genes. These chromatin-tethered kinases have been shown to play both a structural role as part of transcription complexes, as well as an enzymatic role by phosphorylating their target proteins. These findings exemplify the dual role of signalling kinases, demonstrating that they have a more general role as regulators of gene transcription in both higher and lower eukaryotic cells, and act by two distinct mechanisms: (1) cytoplasmic signalling to the nucleus, and (2) as novel class of epigenetic enzymes that directly tether and regulate the epigenome. A detailed understanding of these mechanisms of epigenetic regulation is of particular importance since the reversible nature of epigenetic aberrations makes them attractive targets for the clinical use of epigenetic therapies; for instance, inhibitors of histone modifying enzymes have shown promise as cancer therapeutics, and are effective anti-inflammatory and immunosuppressive drugs. This research topic will present breakthrough gene specific and genome wide studies on the crosstalk between nuclear signaling kinases and epigenetic regulation in two key biological systems: immune system and cancer Keywords biology. Specifically, this topic will feature pioneering work from leading researchers that have contributed to this field in recent years and will feature: (i) overview chromatin, cancer Signalling kinases, epigenetics, immune system, of epigenetic mechanisms in immune system (using T cells as a model system); (ii) the landmark genome wide studies on chromatin anchored signalling kinases in yeast; (iii) novel insights into contributions of chromatin tethered kinases in epigenetic regulation in immune system and cancer; (iv) Field Specialty Section understanding the roles for the nuclear translocation mechanisms; (v) expand the possibilities of new therapeutic strategies using these new epigenetic enzymes.


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