Mechanisms of nuclear transport and interventions
Section snippets
Mechanisms of nuclear transport
Evidence supporting the selective entry of proteins into the nucleus was first suggested by Bonner in 1975. His set of experiments showed that small proteins and nuclear specific proteins, such as histones, accumulate in the nucleus when microinjected into the cytoplasm of Xenopus oocytes. Interestingly, the histones were able to enter the nucleus at an equal or faster rate than some particles of smaller size suggesting the presence of an energy dependent nuclear import pathway. Conversely,
The NPC as a modulator of nuclear transport
Apart from acting simply as an architectural structure through which nuclear transport occurs, the NPC may also play a more dynamic role in regulating transport. In addition to the different substrates recognized by the importins, import and export specificity may also be achieved by altering the nucleoporin expression, thus allowing different interactions between the NPC and karyopherins. The total number of NPCs within the nuclear envelope depends on the cell type and its metabolic activity.
Pharmacological modulation of nuclear import and export
An important aspect of drug action that is often overlooked is that a drug need not directly inhibit, or stimulate, a target’s activity to be effective. Rather, the redistribution or mis-targeting of a drug target, be it an enzyme, structural protein, transport, etc., may have just as profound an effect. The remainder of this review will focus on examples demonstrating this in terms of nuclear localization.
Conclusion
In this review, we have discussed the basic machinery the cell uses for regulating nucleocytoplasmic trafficking as well as some of the chemical compounds and agents that modulate it. Drug action and delivery can take advantage of cellular compartmentation instead of simply blocking enzymatic active sites. Hopefully this review has demonstrated the often-overlooked effectiveness of preventing a molecule from reaching its normal subcellular location. No doubt the development of agents that alter
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