Professor of Biochemistry, Faculty of Medicine & Health Sciences
It is now clear that that transcription factors are a highly diverse group of proteins and phosphorylation is just one of several post-translational modifications that can influence their activity… read more
It is now clear that that transcription factors are a highly diverse group of proteins and phosphorylation is just one of several post-translational modifications that can influence their activity (and that of other signalling components). Our interests have therefore broadened to include STAT3, a signal transducer and activator of transcription also implicated in IEG control but regulated quite unlike Elk-1. As well as phosphorylation we have begun to explore roles for conformational change, oxidation and ubiquitylation in the regulation of these two transcription factors. To complement the biochemical and molecular approaches taken we have also adopted protein mass spectrometry as an important tool both for protein identification and analysis of post-translational modifications.
In previous years the research focus of my lab has been on intracellular signalling by Mitogen-Activated Protein Kinase cascades and how these events lead to changes in expression of specific genes. Most of our work has centred on the interrelationship between the mitogen-sensitive ERKs and Elk-1, one of their nuclear substrates and a member of the ets family of transcription factors. Elk-1 is important in the regulation of several 'immediate early genes' (IEGs) by mitogens at the start of the cell cycle.
The relevance of both Elk-1 and STAT3 function for cell proliferation and thus for cancer studies is manifest. Although our primary goal is to understand the biological mechanisms underlying their regulation we continue to publish in cancer journals. However, the role of STAT3 in cardiac development is a theme in which we have developed a strong interest, particularly with respect to how changes in oxygen tension can modulate gene transcription. On the other hand, Elk-1 is expressed predominantly in regions of the mammalian cortex and, like ERKs, has been implicated in cognitive function. We have therefore begun to examine the regulation of Elk-1 and its brain-specific isoform short Elk in neuronal cells.
University of NottinghamMedical School
Queen's Medical CentreNottingham NG7 2UH
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