University of Dundee

Cancer Biology

Characterisation of enhancer DNA methylation and its impact in gene expression and disease

The School of Life Sciences at the University of Dundee is a world-class academic institution with a reputation for the excellence of its research, its high quality teaching and student experience, and the strong impact of its activities outside academia. With 900 staff from over 60 countries worldwide the School provides a dynamic, multi-national, collegiate and diverse environment with state-of-the-art laboratory, technology and teaching facilities.

Establishing the molecular basis for the therapeutic effect of arsenic trioxide in APL treatment

Arsenic trioxide therapy for Acute Promyelocytic Leukaemia (APL) is mediated by SUMO-dependent degradation of Promyelocytic Leukaemia (PML)-Retinoic Acid Receptor α (RARα) oncogenic fusion protein. We demonstrated (Tatham et al., 2008) that ubiquitin mediated proteolysis of PML requires RNF4 E3 ubiquitin ligase. This allows terminal differentiation of tumour cells and cures disease. The primary effect of arsenic is to dramatically increase the SUMO modification of the PML protein, however the mechanistic basis for remarkable observation remains unclear.