Introduction Proteins accumulate in the nucleus to signal the specific entry of molecules through nuclear pore complex (NPC) [1-3]. This mechanism was observed first in nucleoplasmin, an acidic protein that binds histones H2A and H2B during nucleosome assembly[4-8]. In vertebrates Nuclear pore complex weighs 125Mda in mass and contains 50-100 polypeptides. Thus, for macromolecules to cross the NPC, a signal mediated transport mechanism is required. Although several pathways exist for nuclear transport, classical nuclear localization signals (NLSs) that contain one or more clusters of basic amino acids are well known and characterized [9]. Nuclear localization signals (NLSs) are stretches of residues in proteins that facilitate the import of protein residues into the nucleus. Nuclear localization signal exists in the form of protein peptides bound to carrier proteins for trafficking nuclear proteins into the nucleus. Small molecules less than 40-45kda diffuse freely in and out of the nucleus through nuclear pore complexes between the cytoplasm and the nucleus using soluble carrier proteins [10]. However, the nuclear import of larger molecules, is an energy-dependent process mediated by specific targeting signals called as nuclear localizing sequences (NLSs).[10] These oligopeptides that are less than 10 AAs binds directly to a group of proteins called importins. The structural and functional domains of importin-α consists of a short basic N-terminal called as Importin-β binding domain (11-13) and a large NLS-binding domain of armadillo (Arm) repeats (14). Importin-α transports cargo proteins into the nucleus, and the importin-α is further recognized by importin-β to form a heterotrimer complex that interacts with the hydrop... ... middle of paper ... ...al organs, respectively[52-60]. Trastuzumab conjugated with NLS and labeled with111In using diethylenetriaminepentaacetic acid (DTPA) for receptor-mediated internalisation of the drug by low-energy augur radioimmunotherapy showed increased internalization of 111Intrastuzumab (made of 6 NLS-peptides) in SK-BR-3, MDA-MB-361, and MDA-MB-231 cells from 7.2% ±0.9%, 1.3% ±6 0.1%, and 0.2% ± 0.05% to 14.4%± 6 1.8%, 6.3% ± 0.2%, and 0.9% ±0.2%, respectively [61]. The levels of HER2/neu expression in SK-BR-3, MDA-MB-361, and MDA-MB-231 human breast cancer cells were very high, intermediate and low, respectively [ 61]. Thus, by selectively exploiting the biological property of NLS peptides for enhancing the drug delivery to the target nucleus offers wide range of therapeutic options in chemotherapy, eliciting immunomodulatory effects, and radio immunotherapy.
Glioblastoma Multiforme (GMB) is the most common form of primary malignant brain tumor in adults. With the current standard therapy, median survival time hovers just over 12 months. This incurable disease is devastating with a median survival time of 6-8 months from time of recurrence (J10). The current standard of therapy at first diagnosis consists of surgery followed by radiotherapy with concommittant and adjuvant chemotherapy using the agent temozolamide (TMZ) (Multiple sources). In 2003, the United States Food and Drug administration approved the Gliadel Wafer (GW) for treatment of newly diagnosed GBM (C3). The monoclonal antibody Bevacizumab (BEV) was first used to treat recurrent GBM in 2005 and has a significant survival benefit for patients with grade IV glioma (E5). Many more promising avenues for new treatment have been and are currently being studied. Such areas include the use of antiepileptic drugs, using Convection-Enhanced Delivery of chemotherapeutic agents, and targeting specific molecular markers and pathways such as the epidermal growth factor receptor (EGFR), O6-methylguanine-DNA-methyltransferase (MGMT), and the PI3K/Akt/mTOR pathway.
The first experiment reviewed was titled “MRP3: a molecular target for human glioblastoma multiforme immunotherapy” and was carried out at Duke University Medical Center in Durham, North Carolina by-Kuan et al’s (2010). Their study was conducted to identify brain tumor markers that are needed for prognostics from immunotherapeutic approaches. From series of analysis they found multidrug-resistance protein 3 (MRP3) to be a candidate marker of GBM [2]. After discovering a potential molecular therapeutic target Kuan et al. hypothesize that there would be evidence that MRP3is potentially a good target in immunotherapy for those with GBM [2].
Through its specific interaction with trans retinol, RBP allows this vital nutrient to circulate without appreciable loss. In addition to ligand-binding, RBP interacts with the carrier protein transthyretin (TTR). This protein complex prevents the loss of RBP through glomerular filtration and is also suggested as a vehicle for specific interactions with alleged cell-surface receptors that mediate retinol uptake. In conclusion, retinol-binding protein provides a comprehensive model for the role of proteins as carrier molecules. Structural features such as a characteristic up-and-down beta barrel, disulfide bonds, salt bridges and a hydrophobic core are essential in influencing the complex interactions that are essential to RBP function.
This occurs when special carrier proteins carry solutes dissolved in the water across the membrane by using active transport. When the concentration gradient can not allow travel from one side of the membrane to the other fast enough for the cell’s nutritional needs, then facilitated diffusion is used. The transport protein is specialized for the solute it is carrying, just as enzymes are specialized for their substrate. The transport protein can be
The most important and largest cellular organelle is the nucleus, which houses most of the eukaryotic cell’s DNA and is surrounded by a double membrane. The nucleus contains most of the cells genetic material. The nucleus is the control center of the cell.
Many breast cancers are sensitive to the hormone estrogen. Thus estrogen leads to development of breast cancer tumor formation. Such cancers have cell surface receptors for estrogen. They are called ER-positive cancer or estrogen receptor-positive cancer.
“This knowledge will help us design drugs that mimic the viral effects on these proteins to either activate a host’s immune response or shut it down,” said Dr. Michael Gale, associate ...
The nucleus is one of the most important organelles in a eukaryotic cell. The shape of the nucleus is generally spherical, it should be oval, disc formed reckoning on the sort of cell. The nucleus was found by Robert Brown in 1831 while he was looking at orchids under a microscope. He discovered a blurred area in the cells of the flowers and called it the areola or the nucleus.
Breast Cancer is defined as “a group of solid tumor malignancies arising in the tissues of the breast” (Sarah Crawford, Richard Alder, 2013) in human and other mammals. It can happen to both men and women. For women, breast cancer is one of the leading causes of cancer death. According to National Cancer Institute, in the United States, the 2014 estimated new cases and deaths of female from breast cancer are 232,670 and 40,000, respectively. For male, it’s 430 deaths out of 2,360 new cases. From these numbers, we can see that women in the U.S. are greatly affected by breast cancer, thus, it’s not difficult to imagine the impact on a worldwide level. Although these numbers look frightening, people can actually survive from breast cancer if it is detected early and treated properly, so it is extremely important for all of us, especially women, to have a better understanding of breast cancer.
In the most general terms, the nucleus is the command center of a eukaryotic cell. Although the origin of the organelle is unclear, it is believed that it is derived from a symbiosis relationship between a bacterium and an archaea (Martin W. 2005). Being the main hub for the inner workings of a cell involves different functions overall. These nucleic functions are determined by the genes within the DNA of the cell. Functions of the cell are also regulate by soluble proteins that come in and out of the cell via the membranes and specific channels or the nuclear pore complexes. The overall objectives of the nucleus include; gene expression, compartmentalization, and processing pre-mRNA. The functions of the organelles and sub-regions
The cytoskeleton is a highly dynamic intracellular platform constituted by a three-dimensional network of proteins responsible for key cellular roles as structure and shape, cell growth and development, and offering to the cell with "motility" that being the ability of the entire cell to move and for material to be moved within the cell in a regulated fashion (vesicle trafficking)’, (intechopen 2017). The cytoskeleton is made of microtubules, filaments, and fibres - they give the cytoplasm physical support. Michael Kent, (2000) describes the cytoskeleton as the ‘internal framework’, this is because it shapes the cell and provides support to cellular extensions – such as microvilli. In some cells it is used in intracellular transport. Since the shape of the cell is constantly changing, the microtubules will also change, they will readjust and reassemble to fit the needs of the cell.
In this step, large ribosomal subunit protein L7/L12 stalk (L7 differs from L12 by an acetylated N terminus) interacts with helix D of EF-Tu, using its flexible C-terminal domain and delivers the ternary complex to the A-site of the ribosome, shown in figure 11. The stalk is made of two L7/L12 dimers. The N-terminal domain aids in formation of the dimer and anchoring the protein to the ribosomes whereas the C-terminal domain binds to EF-Tu in the ternary complex (Savelsbergh et al., 2000).
Nutrients are the chemicals that humans need to live and grow. Humans obtain their nutrients from the food and water that they drink. They are used to build and repair tissues and regulate body processes and are converted to and used as energy. Lipids are a category of nutrients. Lipids consist of fats, oils, and waxes and are very important for are body’s health. Lipids are important for the human body because they are for storing energy, they’re good at storing energy because they can concentrate a group of calories in a smaller area.
The nucleus is often the largest organelle found in a Eukaryotic cell with a size of 10-20 un. It is surrounded by two membrane layers which can be identified on the diagram below. Within the nucleus structure are small pores with a size of 100un in diameter. These pores together make up around one third of the nuclear membrane surface area.
...radient within the thylakoid membrane. The hydrogen atoms find a protein channel (ATP synthase) to pump them out of the thylakoid called facilitated diffusion. The hydrogen flows through the ATP synthase, which is used as energy, and then they tie the ADP with phosphate to create ATP. The hydrogen atoms travel through the ATP synthase and connect NADP+ to create NADPH.