Nuclear targeting

Allen, P. B., Kwon, Y. G., Naim, A. C. and Greengard, P. Isolation and characterization of PNUTS, a putative protein phosphatase 1 nuclear targeting subunit. J. Biol. Chem. 273 4089-4095,1998. 

NSF N-ethylmaleimide-sensitive factor PNUTS phosphatase 1 nuclear targeting subunit... 

Robbins, J., Dilworth, S., Laskey, R., and Dingwall, C. (1991). Two interdependent basic domains in nucleoplasmin nuclear targeting sequence identification of a class of bipartite nuclear targeting sequences. Cell 64, 615-623. 

Stoka, V., Turk, B., Schendd, S.L., Kim, T.-H., Cirman, T, Srripas, SJ., EUerby, L.M., Bredesen, L., Freeze, H, Abrahamson, M., Bromme, D., Krajewski, S., Reed, J.C., Yin, X.-M., Turk, V., and Salvesen G.S., 2001, Lysosomal Protease Pathways to Apoptosis. Cleavage of Bid, not pro-caspases, is the most likely route. J. Biol. Chem. 276 3149-3157 Srm, X. and Ross, D., 1996, Quinone-induced apoptosis in human colon adenocarcinoma ceUs via DT-diaphorase mediated bioactivation. Chem. Biol. Interact. 100 267-76 Taatjes, D.J. and Koch, T.H., 2001, Nuclear targeting and retention of anthracycUne antitumor dmgs in sensitive and resistant tumor ceUs. Curr. Med Chem. 8 15-29 Tarr, M. and van Helden, PT)., 1990, Inhibition of transcription by adriamycin is a... 

To bridge this gap, liposomal transfection efficiency can be dramatically enhanced by the inclusion of peptides into the complex without increasing immunogenicity. Peptides can be selected to assist lipofection at each key stage of the process complex formation, cell targeting and uptake, endosomal disruption, and nuclear targeting. The purpose of this chapter is... 

Jans DA, Xiao CY, Lam MH. Nuclear targeting signal recognition a key control point in nuclear transport Bioessays 2000 22(6) 532-544. 

Chan CK, Jans DA. Using nuclear targeting signals to enhance non-viral gene transfer. Immunol Cell Biol 2002 80(2) 119-130. 

Subramanian A, Ranganathan P, Diamond SL. Nuclear targeting peptide scaffolds for lipofection of nondividing mammalian cells. Nat Biotechnol 1999 17(9) 873-877. 

Vaysse L, Harbottle R, Bigger B, et al. Development of a self-assembling nuclear targeting vector system based on the tetracycline repressor protein. J Biol Chem 2004 279(7) 5555-5564. 

Reed MW, et al. Synthesis and evaluation of nuclear targeting peptide-antisense ohgodeoxynucleotide conjugates. Bioconjug Chem 1995 6 101-108. 

In mammalian cells the El ubiquitin-activating enzyme exists in two isoforms, Ela (110 kDa) and Elb (117 kDa), which are derived from a single gene and mRNA (Cook and Chock 1992, Handley Gearhart et al. 1994). The isoform Ela is predominantly found in the nucleus and has been shown to harbor a functional nuclear localization sequence (NLS) required for nuclear targeting and phosphorylation. In contrast, Elb lacks the NLS, is not phos-phorylated and localized in the cytoplasm (Handley-Gearhart et al. 1994 Stephen et al. 1997). Phosphorylation of Ela was demonstrated to occur in a cell cycle-dependent manner, being maximal in G2 phase (Stephen et al. 

Stephen AG, Trausch Azar JS, Ciechanover A, Schwartz AL (1996) The ubiquitin-activating enzyme El is phosphorylated and localized to the nucleus in a cell cycle-dependent manner. Biol Chem 271 15608-15614 Stephen AG, Trausch Azar JS, Handley Gearhart PM, Ciechanover A, Schwartz AL (1997) Identification of a region within the ubiquitin-activating enzyme required for nuclear targeting and phosphorjdation.) Biol Chem 272 10895-10903 Sternsdorf T, Jensen K, Will H (1997) Evidence for covalent modification of the nuclear dot-associated proteins PML and SplOO by PICl/SUMO-1. J Cell Biol 139 1621-1634... 

Chaperone, assists in T-DNA trafficking Involved in nuclear targeting of T-complex Involved in mediating targeted proteolysis... 

Free, isolated neutrons have a half-life of 12 8 mm If you produce 104 neu trons in a pulsed nuclear target experiment, how long will you have to wait until only 10 neutrons remain (statistically) 1... 

Poly (ADP-ribose). A eukaryotic peculiarity, which is not well understood, is the synthesis of poly(ADP-ribose) chains attached to many sites in nuclear proteins (see also Eq. 15-16). Increased synthesis is observed following damage to DNA.761 763a The poly (ADP-ribose) polymerase binds to DNA near strand breaks or nicks and, using NAD+ as a substrate, synthesizes the highly branched polymer attached to a small number of nuclear target proteins. 

Nikolic, B., MacNulty, E., Mir, B., and Wiche, G. (1996). Basic amino acid residue cluster within nuclear targeting sequence motif is essential for cytoplasmic plectin-vimentin network junctions./. Cell Biol. 134, 1455-1467. 

The cellular space, encompassed by the plasma membrane and excluded by organelles and the cytoskeleton, is occupied by the cytoplasm containing macromolecules and small organic and inorganic solutes. Considering that plasmid DNA has to escape from the endocytic vesicles, which are distributed throughout the cytoplasm randomly, it is reasonable to assume that the diffusional mobility of the DNA is an important determinant of the nuclear targeting efficiency of DNA. 

While isolation of a specific inhibitor will be necessary to assess the definitive role of the cytosolic nuclease in the low transfection efficiency in vivo, circumstantial evidence suggests that the metabolic instability of plasmid DNA represents one of the cellular barriers to gene transfer. Microinjection of DNA complexes with PEI has augmented the transfection efficiency (Pollard et al., 1998). Although the stability of the PEI-complexed DNA has not been determined in vivo, it has been demonstrated that the nuclease resistance of plasmid DNA is dramatically increased upon complex formation in vitro (Cappaccioli et al., 1993 Chiou et al., 1994 Thierry et al., 1997). Therefore, it is conceivable that faster diffusional mobility and decreased nuclease susceptibility jointly lead to the enhanced nuclear targeting efficiency of the PEI-condensed plasmid DNA. 

Viruses are complex particles, entering the cells by fusion of their envelope to the plasma membrane or by endocytosis followed by the escape of the capsid by membrane fusion or lysis (Sodeik, 2000). The diameter of the viral particle could be several hundred nanometers, implying a very inefficient diffusional movement in the cytoplasm, based on those physicochemical considerations that were discussed above (Kasamatsu and Nakanishi, 1998). Despite these limitations, those viruses that replicate in the nucleus have evolved sophisticated mechanisms to ensure a highly efficient nuclear delivery of their genetic material. Since these mechanisms may provide a conceptual framework to design novel non-viral delivery systems, we shall review some of the key elements that account for the nuclear targeting of certain viruses. 

Nakanishi, A., Clever, J., Yamada, M., Li, P.P. and Kasamatsu, H. (1996) Association with capsid protein promotes nuclear targeting of simian virus 40 DNA. Proc. Natl. Acad. Sci. USA, 93, 96-100. 

Neves, C., Escriou, V., Byk, G., Scherman, D. and Wils, P. (1999) Intracellular fate and nuclear targeting of plasmid DNA. Cell Biol. Toxicol., 15, 193-202. 

---