Nuclear localization signals

Organometaiiic Derivatives of Other Peptides 5.3.3.1 Nuclear Localization Signal 

The prudent choice of appropriate side chain protecting groups for Lys and Arg did pose a particular problem in combination with the chemical stability of the metallocenes and available resins and linkers. In order to study cellular uptake and localization in the nucleus of living cells, derivatives of 36 and 37 with an additional fluorescent dye attached to the peptide were also prepared. Cellular uptake and localization of these conjugates was then followed in different cell lines by fluorescence microscopy. This is the first study of sub-cellular localization of organometaiiic peptide derivatives with non-radioactive metals (see also Section 5.5.3.2 below for an example ofa dual radiometal- and fluorescent-labeled peptide). 

---

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). 

CuTRONA G., Carpaneto E.M., Ulivi M., Roncella S., Landt O., Ferrarini M., Boeea L. C. Effects in live cells of a c-myc anti-gene PNA linked to a nuclear localization signal. Nature Biotechnol. 

Figure 43-10. Regulation of the NF-kB pathway. NF-kB consists of two subunits, p50 and p65, which regulate transcription of many genes when in the nucleus. NF-kB Is restricted from entering the nucleus by IkB, an Inhibitor of NF-kB. IkB binds to—and masks—the nuclear localization signal of NF-kB.

NLS, nuclear localization signal PTS, peroxisomal-matrix targeting sequence. 

Zanta MA, Belguise VP, Behr JP (1999) Gene delivery a single nuclear localization signal peptide is sufficient to carry DNA to the cell nucleus. Proc Natl Acad Sci USA 96 91-96... 

Branden LJ, Mohamed AJ, Smith Cl (1999) A peptide nucleic acid-nuclear localization signal fusion that mediates nuclear transport of DNA. Nat Biotechnol 17 784-787... 

Nagasaki T, Myohoji T, Tachibana T, Futaki S, Tamagaki S (2003) Can nuclear localization signals enhance nuclear localization of plasmid DNA Bioconjug Chem 14 282-286... 

Nuclear ion stopping, 74 433 Nuclear localization signal (NLS), 26 451 Nuclear magnetic resonance (nmr), 7 7 418 27 278. See also Deuterium nmr... 

Holtz, D., Tanaka R., Hartwig, J., and McKeon, F. (1989). The CaaX motif of lamin a functions in conjunction with the nuclear localization signal to target assembly to the nuclear envelope. Cell 59, 969-977. 

Figure 2. Structural and functional domains of PARP-1. PARP-1 has a highly conserved structural and functional organization including (1) an N-terminal DNA binding domain with two Cys-Cys-His-Cys zinc finger motifs (FI and Fll), (2) a nuclear localization signal (NLS), (3) a central automodification domain containing a BRCT ( BRCAl C-terminus-like ) protein-protein interaction motif, and (4) a C-terminal catalytic domain with a contiguous 50 amino acid sequence, the PARP signature motif, that forms the active site...

Truant R, Cullen BR. The arginine-rich domains present in human immunodeficiency virus type 1 TAT and Rev function as direct importin beta-dependent nuclear localization signals. Mol Cell Biol 1999 19(2) 1210-1217. 

Hebert E. Improvement of exogenous DNA nuclear importation by nuclear localization signal-bearing vectors a promising way for non-viral gene therapy Biol Cell 2003 2 95(2) 59-68. 

Cartier R, Reszka R. Utilization of synthetic peptides containing nuclear localization signals for nonviral gene transfer systems. J Biol Chem 2002 9(3) 157-167. 

Ma H, Zhu J, Maronski M, et al. Non-classical nuclear localization signal peptides for high efficiency lipofection of primary neurons and neuronal cell lines. Neuroscience 2002 112(l) l-5. 

The El protein is highly conserved through evolution. For example, human and yeast Els are 53% identical. El contains a nuclear localization signal and is found in the nucleus in addition to other subcellular compart-... 

This enzyme is also known to be phosphorylated and translocated to the nucleus in a cell cycle-dependent fashion. Since only phosphorylated form of El is translocated to the nucleus despite the presence of the nuclear localization signal in the El sequence, it is conceivable that phosphorylation is an obligatory additional signal for nuclear localization. Evidence obtained by Stephen et shows that phosphorylation facilitates either transport to the nucleus or its retention in the nucleus. 

Knuehl C, Seelig A, Brecbt B, Henklein P, Kloetzel PM (1996) Functional analysis of eukaryotic 20S proteasome nuclear localization signal. Exp Cell Res 225 67-74 Koegl M, Hoppe T, Schlenker S, Ulrich HD, Mayer TU, Jentsch S (1999) A novel ubiquitination factor, E4, is involved in multiubiquitin chain assembly. Cell 96 635-44... 

---