title: Nuclear localization signals (NLS).
abstract: Available data strongly suggest that simple karyophilic clusters of arginines and lysines in nucleus-targeted proteins signal the anchoring of these proteins to specialized transporter molecules found on the pore complex or in the cytoplasm. These peptides have been termed nuclear localization signals (NLS). Other nuclear proteins contain "split" or "bipartite" NLS hypothesized to be reconstituted by protein folding or conformational change induced by glucocorticoids. The active NLS needs to be exposed to the protein surface, the cell has invented mechanisms to expose a hidden or cryptic NLS by protein phosphorylation, dephosphorylation, dissociation of an inhibitory subunit that masks the NLS, processing of a larger precursor, and binding of a hormone to regulate the nuclear import of a protein transcription factor at a certain stage of development, or cell cycle. It is proposed (1) that a hexapeptide with four arginines and lysines (and histidines, in some cases) is a good candidate for a "core NLS," (2) that acidic domains on proteins to be imported may participate in anchoring them to the transporter cytoplasmic or pore complex NLS-receptor, and (3) that NLS have both a cytoplasmic and a nuclear function. The interaction between nuclear proteins and transporter proteins in the pore appears to be largely electrostatic and to be disrupted by the binding of mRNA molecules to the same transporter protein, functioning also for the cytoplasmic export of RNA.
authors.affiliation: Institute of Molecular Medical Sciences, Palo Alto, CA 94306.
authors.forename: T
authors.initials: T
authors.lastname: Boulikas
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002467:Cell Nucleus / Q000378:metabolism*; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008969:Molecular Sequence Data; D010766:Phosphorylation; D021382:Protein Sorting Signals / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D021382:Protein Sorting Signals; D014157:Transcription Factors