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Pathways Mechanism of Protein Import into the Nucleus
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October 2003
Description: Description: Nuclear pore complexes (NPCs) are large proteinaceous assemblies that provide the only known portals for exchanging macromolecules between the nucleus and cytoplasm. This includes the movement of small molecules and the selective, facilitated transport of large proteins and RNAs. Faithful, continuous NPC assembly is key for maintaining normal physiological function and is closely tied to proper cell division. One of the unexpected developments during the past decade was the realization that the NPC itself probably does not function primarily as a gating mechanism or by directly transporting cargo macromolecules between the nuclear and cytoplasmic compartments. Instead, nuclear trafficking relies on a range of soluble components. Transport factors bind their cargo in one compartment and then move through the NPCs to the other compartment, where the cargo is released. The transport factor then recycles back through the NPC to participate in another round of transport. In many instances, this process is orchestrated by the Ras-superfamily GTPase Ran. Bischoff et al. describe in detail how the nucleotide state of Ran is controlled by its nuclear guanine-nucleotide-exchange factor (RCC1) and cytoplasmic GTPase-activating protein (RanGAP). The nucleotide state of Ran is crucial to defining the interactions between transport factors, their cargoes and nucleoporins, and is fundamental to the sorting mechanism that defines the directionality of transport.
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references: references: BB Quimby and AH Corbett Nuclear transport mechanisms. Cell Mol Life Sci, Nov 2001; 58(12-13): 1766-73.

E Kiseleva, MW Goldberg, J Cronshaw, and TD Allen The nuclear pore complex: structure, function, and dynamics. Crit Rev Eukaryot Gene Expr, Jan 2000; 10(1): 101-12.

Ian G. Macara Transport into and out of the Nucleus Microbiol. Mol. Biol. Rev., Dec 2001; 65: 570 - 594.

Michael P. Rout and John D. Aitchison The Nuclear Pore Complex as a Transport Machine J. Biol. Chem., May 2001; 276: 16593 - 16596.


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