Therapeutic targeting of nuclear protein import in pathological cell conditions.

Proteins enter the nucleus through the nuclear pore complex. Once in the nucleus, some proteins, such as transcriptional regulators, can turn genes on or off, and change the composition of the cell and its function to meet the demands of its environment. This process of protein import into the nucleus is highly controlled and regulated by the expression or function of single cargoes, transport receptors, or the transport channels themselves. Thus, these components of the import process have an impact on transport capacity, which subsequently affects gene expression, signal transduction, and cell growth and development. With such a key position in the process of cell growth, it is reasonable to hypothesize that alterations in nuclear protein transport may play an important role in pathological cell conditions that have abnormal cell growth as a central feature. Indeed, there are now sufficient data to demonstrate that alterations in nuclear protein transport participate in alterations in cell proliferation and hypertrophy. Further study is needed to provide definitive proof that changes in nuclear protein import directly participate in the pathogenesis of diseases such as hypertension, atherosclerosis, cancer, viral infection, and diabetes. However, the data to date have, on select occasions, led to a clear association of alterations in nuclear transport with disease states. Furthermore,this research has led to the important identification of new targets within the process of nuclear protein import that hold therapeutic promise to inhibit viral replication, to improve drug delivery during cancer therapy, and, in general, to modify cell growth and viability during disease conditions.