Role of the tumor suppressive E3 ubiquitin-protein ligase, Hace 1, in the development of childhood neoplasm

The onset and growth of a tumour may be due to the destruction of the balance that is normally achieved between tumour promoting and tumour suppressing factors. Recently, Dr. Poul Sorenson’s research team discovered a new gene, Hace1, from a case of Wilms' tumour (the most common kidney tumour of childhood). They also found that Hace1 protein levels were reduced in 75% of the Wilms' tumours analyzed, and that the restoration of Hace1 levels in tumour cells was capable of inhibiting tumour growth. These findings suggest that Hace1 is a tumour suppressive factor and that loss of Hace1 may contribute to the development of childhood tumours. However, the mechanisms by which Hace1 inhibits tumour formation are not yet understood. Current research suggests that Hace1 is an enzyme that specifically labels target proteins with small protein tag(s) called ubiquitin. It is thought that alterations of this process, as in the reduction of Hace1 levels observed in Wilms’ tumour, may lead to malfunctions of the target proteins and facilitate tumour development. Dr. Fan Zhang is testing this hypothesis through the identification of Hace1 target proteins and analysis of the Hace1 function in both normal and tumour cells. The knowledge derived from this study will help researchers understand how loss of Hace1 leads to the formation of childhood tumours which, in turn, may lead to new preventive treatment based on correcting the imbalance between tumour promoting and tumour suppressive factors.