Nuclear-cytoplasmic transport as novel therapeutic target.

The nuclear-cytoplasmic transport of macromolecules across the nuclear membrane is mediated by carrier proteins called karyopherins. There are about 18 karyopherins (11 importins and 7 exportins) each recognizing a unique set of proteins or RNAs, thus creating multiple transport pathways across the nuclear membrane. The correct nuclear-cytoplasmic transport of macromolecules across the nuclear membrane is central to the biology of the cell. Alterations in this process have been observed in various types of cancer cells and modulating the nucleocytoplasmic transport of cargos, generally or specifically for one cargo, would constitute an elegant way to stimulate or inhibit aberrant signaling pathways of interest in defined cancers. In the proposed project we wish to identify and validate novel molecular targets within the different cellular nuclear transport pathways that can form the basis of new therapies for cancer.