Human papillomaviruses Vousden's early work focused on the
molecular biology of
human papillomaviruses (HPVs), which are associated with
cervical cancer. With Douglas Lowy and others, she pinpointed the specific viral
oncoproteins required by HPV-16 to
immortalise epithelial cells. She was also part of a group which showed that E6, one of the HPV-16 oncoproteins, binds to the human
tumour suppressor protein
p53 in vivo, resulting in its degradation.
p53 suppressor protein Vousden's recent research has centred on
p53, To prevent it being activated inappropriately, p53 is strictly controlled in the normal cell. Vousden discovered that a key element in this regulation is the protein
Mdm2. With Allan Weissman and others, she showed that Mdm2 is a
ubiquitin ligase which targets p53 for degradation by the
proteasome, thus ensuring levels of the protein remain low when the cell is not under stress. Reactivating p53 can inhibit the growth of some tumours, making Mdm2 an attractive target for cancer therapeutics. As Mdm2 targets only a small number of proteins for destruction, an inhibitor might have few side effects. A major focus of Vousden's recent work has been investigating the structure of Mdm2 and seeking molecules that inhibit it; a group of low-molecular-weight compounds (discovered in collaboration with the Department of Chemistry at the
University of Glasgow) have recently shown promise in cell-culture studies. Mdm2 inhibitors have also been discovered by researchers at
Hoffmann–La Roche and the
Karolinska Institute.
Key publications • • • Peters G, Vousden KH, eds.
Oncogenes and Tumour Suppressors (Oxford University Press; 1997) () • • • • • • ==Awards and honours==