Transcriptional regulation by the Wilms' tumour suppressor protein WT1

Wilms' tumour is a paediatric malignancy of the kidneys and is the most common solid tumour found in children. The Wilms' tumour suppressor protein WT1 is mutated in approx. 15% of Wilms' tumours, and is aberrantly expressed in many others. WT1 can manifest both tumour suppressor and oncogenic activities, but the reasons for this are not yet clear. The Wilms' tumour suppressor protein WT1 is a transcriptional activator, the function of which is under cell-context-specific control. We have previously described a small region at the N-terminus of WT1 (suppression domain) that inhibits the transcriptional activation domain by contacting a co-suppressor protein. We recently identified BASP1 as one of the components of the co-suppressor. Here, we analyse the mechanism of action of the WT1 suppression domain, and discuss its function in the context of the role of WT1 as a regulator of development.