Mechanisms of nuclear transport and interventions

One of the more overlooked aspects of drug action and delivery is the exploitation of nucleocytoplasmic shuttling. Eukaryotic cells regulate many biological processes by the compartmentation of specific proteins into designated areas. Drugs that have a direct effect on a single protein must be able to localize to the same site as the protein and interact with one or more of its domains. Alternatively, a drug that effectively blocks the target protein from reaching its proper organelle can also inhibit the protein's function. Exploiting the selective movement of macromolecules across the nuclear envelope represents an exciting new area of drug development. This review aims to explain the basic nuclear import/export pathways while focusing on the known drugs that alter the regulation of nucleocytoplasmic trafficking. (C) 2003 Elsevier Science B.V. All rights reserved.