Dr Stefan Roberts
Reader in Cancer Biology
School of Cellular and Molecular Medicine,
University of Bristol, Medical Sciences Building,
Bristol, BS8 1TD
phone: +44 (0)117 33 12062 (internal 12062)
group: Gene expression lab
Mechanisms of transcriptional regulation in mammalian cells
Transcription is at the heart of gene expression and is subject to strict control. The aberrant function of transcriptional regulators is associated with many cancers. How transcriptional regulators function is the focus of research in this laboratory. Our studies concern two major project areas;
1. Transcriptional regulation by the Wilms' tumour suppressor protein WT1
The transcriptional regulator WT1 is mutated in the paediatric cancer Wilms' tumour, and has also been linked with many other malignancies including Leukaemia, breast and lung cancer. The mechanism of action of WT1 is complex, having both transcriptional activation and repression activities. We are studying the transcription function of WT1 and how this changes in cancer. We are particularly interested in the WT1 cofactor, BASP1, which converts WT1 from a transcriptional activator to a repressor.
2. Regulation of the general transcription machinery
We are studying the mechanisms by which activator proteins stimulate transcription in mammalian cells. This involves both a biochemical approach and the use of in vivo transcription systems. A crucial function of transcriptional activators is the recruitment of the general transcription factor TFIIB to the promoter and is the subject of research in our laboratory.
- Shandilya, J., Wang, Y. and Roberts,S.G.E. (2012). TFIIB dephosphorylation links transcription inhibition with the p53-dependent DNA damage response. Proceedings of the National Academy of Sciences USA 109, 18797-18802.
- Toska, E., Campbell, H.A., Shandilya, J., Goodfellow, S.J., Shore, P., Medler, K.F. and Roberts, S.G.E. (2012). Repression of transcription by WT1-BASP1 requires the myristoylation of BASP1 and the PIP2-dependent recruitment of histone deacetylase. Cell Reports 2, 462-469.
- Essafi, A., Webb, A., Berry, R.L., Slight, J., Burn, S.F., Spraggon, L., Velecela, V., Martinez-Estrada, O.M., Wiltshire, J.H., Roberts, S.G.E., Davies, J.A., Hastie, N.D. and Hohenstein, P. (2011). A WT1-controlled chromatin switching mechanism underpins tissue-specific Wnt4 activation and repression. Developmental Cell 21, 559-574.
- Goodfellow, S.J., Rebello, M.R., Zeef, L.A.H., Toska, E., Rudd, S.G., Medler, K.F. and Roberts, S.G.E. (2011). WT1 and its transcriptional cofactor BASP1 redirect the differentiation pathway of an established blood cell line. Biochemical Journal 435, 113-125.
- Hartkamp, J., Carpenter, B. and Roberts, S.G.E. (2010). The Wilms' Tumor suppressor protein WT1 is processed by the serine protease HtrA2/Omi. Molecular Cell 37, 159-171.
- Wang. Y., Fairley, J.F. and Roberts, S.G.E. (2010). Phosphorylation of TFIIB links transcription initiation and termination. Current Biology 20, 548-553.
View all publications held on the University of Bristol's IRIS database
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