Protein import, nucleus sequence

Figure 12.8 Model for general and cell-specific plasmid nuclear import. (A) SV40 enhancer-mediated nuclear import. Because the transcription factors bound by this DNA sequence are ubiquitously expressed, SV40 DNA localizes to the nuclei of all cell types (see Table 12.1). (B) Smooth muscle-specific plasmid nuclear import. Smooth muscle-specific transcription factors, including SRF among others, can bind to their target sites within the SMGA promoter carried on a plasmid and serve to transport the DNA to the nucleus via interactions with the NLS-mediated protein import machinery. Since these factors are not expressed in other cell types, no nuclear import will occur in non-smooth muscle cells.

Proteins Imported to or exported from the nucleus contain a specific amino acid sequence that functions as a nuclear-localization signal (NLS) or a nuclear-export signal (NFS). Nucleus-restricted proteins contain an NLS but not an NES, whereas proteins that shuttle between the nucleus and cytoplasm contain both signals. 

Importins are transport proteins at the nuclear pore complex, needed for the selective import of proteins into the nucleus. They recognize nuclear localization signal sequences of cargo proteins. 

Sequence of amino acids that determine the transport of proteins into the nucleus. Although there is no clear consensus, nuclear localization signals tend to be rich in positively charged residues, which allow interaction with proteins from the nuclear import machinery (i.e., importins). 

In most multicellular eukaryotes, the nuclear envelope breaks down at each cell division, and once division is completed and the nuclear envelope reestablished, the dispersed nuclear proteins must be reimported. To allow this repeated nuclear importation, the signal sequence that targets a protein to the nucleus—the nuclear localization sequence, NLS—is not removed after the protein arrives at its destination. An NLS, unlike other signal sequences, may be located almost anywhere along the primary sequence of the protein. NLSs can vary considerably, but many consist of four to eight amino acid residues and include several consecutive basic (Arg or Lys) residues. 

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