Abstract
Entry into the eukaryotic cell nucleus occurs through multiple pathways involving specific targeting signals, and intracellular receptor molecules of the importin/karyopherin superfamily which recognise and dock the nuclear import substrates carrying these signals at the nuclear pore. Subsequent to translocation through the pore via a series of importin-mediated docking steps at multiple sites within it, release into the nucleus is effected by the monomeric guanine nucleotide binding protein Ran. Different importins possess distinct target sequence-binding specificities, meaning that different importins mediate the nuclear import of different classes of proteins. This extends to different classes of transcription factors which are recognised by distinct importins, and whose transport to the nucleus is modulated by specific regulatory mechanisms. The first step of nuclear import is of central importance, with the affinity of the importin: targeting signal interaction being a critical parameter in determining transport efficiency. In the whole cell context, target signal recognition can be modulated through differential expression of the importins themselves, as well as through competition between different importins for the same nuclear import substrate, and between different nuclear import substrates for the same importin. In addition, there are specific mechanisms to modulate targeting sequence-importin interaction directly through phosphorylation. The fact that there are distinct nuclear import pathways for different types of nuclear import substrates enables the cell to regulate these pathways specifically, ensuring efficient nuclear import of particular proteins as and when required.
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Jans, D.A., Forwood, J.K. (2005). Nuclear Protein Import. In: Nuclear Import and Export in Plants and Animals. Molecular Biology Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/0-387-27747-1_9
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DOI: https://doi.org/10.1007/0-387-27747-1_9
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