The London Research Institute research groups are based at Lincoln’s Inn Fields and Clare Hall. Our major research themes are: the biology of tumours and tissues, cellular regulatory mechanisms and genomic integrity and cell cycle.
Richard Treisman : Signal Transduction and Transcription
Goals
Previous and current research
We study the mechanisms by which cellular signal transduction pathways cause specific activation of gene transcription. We focus on the transcriptional regulator SRF, first identified through our studies of the c-fos proto-oncogene, which controls both growth factor-regulated and muscle-specific genes. SRF activity is regulated by association with different cofactors. The Ternary Complex Factor (TCF) family of Ets domain proteins - SAP-1, Elk-1 and Net - are controlled through MAP kinase signal pathways. In contrast, members of the Myocardin Related Transcription Factor (MRTF) family - MAL/MKL1, MAL16/MKL2 and myocardin - are either regulated through Rho GTPase signalling (MAL and MAL16), or apparently act constitutively (Myocardin). Our current research on the SRF system focuses on the molecular analysis of these regulatory cofactors, and their role in processes controlled by Rho GTPases, such as adhesion and motility. Research on the TCF family is aimed at the elucidation of the SAP-1 gene to developmental processes. A developing research interest in the laboratory is the role played by SRF and its cofactors in T cell development and immune function.
Future projects
Regulation of SRF activity by Rho GTPases occurs through their ability to induce changes in actin dynamics, specifically depletion of the G-actin pool. We recently showed that the MAL protein associates with G-actin through a novel sequence motif, and its accumulation in the cell nucleus is induced by changes in actin dynamics.
Selected Papers
Mouilleron S, Langer CA, Guettler S, McDonald NQ, Treisman R. Structure of a Pentavalent G-Actin:MRTF-A Complex Reveals How G-Actin Controls Nucleocytoplasmic Shuttling of a Transcriptional Coactivator. Sci Signal. 2011;4(177):ra40
(Abstract)
Mylona A, Nicolas R, Maurice D, Sargent M, Tuil D, Daegelen D, Treisman R, Costello P.The essential function for SRF in T cell development reflects its specific coupling to ERK signalling. Mol and Cell Biol. 2010;31(2):267-76
(Abstract)
Costello P, Nicolas R, Willoughby J, Wasylyk B, Nordheim A, Treisman R. Ternary complex factors SAP-1 and Elk-1, but not net, are functionally equivalent in thymocyte development. J Immunol. 2010;185(2):1082-92
(Abstract)
Pawłowski R, Rajakylä EK, Vartiainen MK, Treisman R. An actin-regulated importin alpha/beta-dependent extended bipartite NLS directs nuclear import of MRTF-A. EMBO J. 2010;29(20):3448-58
(Abstract)
Vartiainen MK, Guettler S, Larijani B, Treisman R. Nuclear actin regulates dynamic subcellular localization and activity of the SRF cofactor MAL. Science. 2007;316(5832):1749-52
(Abstract)
Miralles F, Posern G, Zaromytidou AI, Treisman R. Actin dynamics control SRF activity by regulation of its coactivator MAL. Cell. 2003;113:329-342
(Abstract)
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Richard Treisman
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