3. Dissecting the molecular function of the oncogenic nucleoporin Nup88 in the p53 and pRB tumour suppressor pathways
The nucleoporin Nup88 is overexpressed in a vast number of human tumours, and these tumours are characterized by their aggressiveness and high frequency of metastasis. How Nup88 overexpression is related to cellular transformation, however, has remained elusive. We have set up a model system to study Nup88 function in a non-tumour background and found that overexpression of Nup88 causes both inhibition of apoptosis and enhanced proliferation. We have evidence that the two major tumour suppressor pathways, the p53 and the pRb pathway, are impaired in the presence of enhanced levels of Nup88 and are now aiming to understand this on the molecular level.