Protein targeting nuclear proteins

Tf-containing PEG-shielded polyplexes have also been applied for systemic tumor-targeted delivery of siRNA [106-108]. Systemic treatment of Neuro 2A tumorbearing mice using Tf-PEG-shielded crosslinked oligoethylenimines for delivery of siRNA against Ras-related nuclear protein (Ran) led to >80% reduced Ran protein expression, associated with tumor apoptosis and reduced tumor growth [108]. 

Most of the mitochondrial proteins are nuclear encoded and thus must be targeted into mitochondria and sorted into some of their components after their synthesis at the cytosol. Because mitochondria have two membranes, there are four localization sites the matrix, the inner membrane, the intermembrane space, and the outer membrane (Fig. 6). Although there has been considerable progress in our understanding of these processes, some questions still remain. Moreover, the total picture is rather complicated and contains many exceptions. A simplified view is presented here based mainly on the view of Pfanner and Mihara (Mihara and Omura, 1996 Pfanner et al., 1997 Pfanner, 1998). There are also a number of other excellent reviews on this subject (Schatz, 1996 Stuart and Neupert, 1996 Neupert, 1997 Roise, 1997). 

Smith, H., and Raikhel, N. (1999). Protein targeting to the nuclear pore. What can we learn from plants Plant Physiol. 119, 1157-1163. 

In addition to being used for structural determinations of protein targets, NMR is increasingly being used to examine the dynamic interactions of ligand-receptor binding. Two NMR properties are particularly important chemical shift and nuclear spin relaxation. 

Morgan-Lappe SE, Tucker LA, Huang X et al (2007) Identification of Ras-related nuclear protein, targeting protein for xenopus kinesin-like protein 2, and stearoyl-CoA desaturase 1 as promising cancer targets from an RNAi-based screen. Cancer Res 67 4390-4398... 

Chemoradiation in Cancer Therapy, edited by Hak Choy, 2003 Fluoropyrimidines in Cancer Therapy, edited by YoucefM. Rustum, 2003 Targets for Cancer Chemotherapy Transcription Factors and Other Nuclear Proteins,... 

FIGURE 2.2 The anatomy of the neuron. Communication between two neurons occurs at the synapse. The presynaptic neuron produces and releases the neurotransmitter into the synaptic cleft. Four mechanisms (1 ) are important to understand the function of most neurotransmitter systems. The release of neurotransmitter can be modulated via presynaptic receptors (1). The amount of neurotransmitter in the synaptic cleft can be decreased by reuptake into the presynaptic neuron (2) or via enzymatic degradation. Neurotransmitter effects at the target neuron are relayed via fast-acting ion channel—coupled receptors (3) or via slower-acting G protein—coupled receptors (4). Down-stream effects of postsynaptic receptors include the phosphorylation (P) of nuclear proteins. 

Biomaterials such as proteins/enzymes or DNA display highly selective catalytic and recognition properties. Au nanoparticles or nanorods show electronic, photonic and catalytic properties. The convergence of both types of materials gives rise to Au NP-biomolecule hybrids that represent a very active research area. The combination of properties leads to the appearance of biosensors due to the optical or electrical transduction of biological phenomena. Moreover, multifunctional Au NP-peptide hybrids can be used for targeting nuclear cells where genetic information is stored and could be useful for biomedical applications [146]. 

---