The WT1 protein plays multiple roles in both cancer and the kidney and interacts with a number of proteins to function as a molecular ‘switch’ that turns genes on and off. In this proposal we will use the zebrafish model and cell culture to examine the importance of two WT1-interacting proteins: WTX, implicated in kidney cancer, and NFE2L1, a regulator of the cell’s ‘trash can’ called the proteasome. We will confirm that WT1 physically interacts with WTX and NFE2L1, and explore its effect on the activation of the proteasome genes. We hypothesise that cancers turn on WT1 in order to dampen the proteasome so that pro-growth/survival proteins accumulate. A better understanding of this new role for WT1 will help develop new treatments for cancer and kidney diseases in the future.