In addition, USP7 is involved in the stabilization of the tumor suppressor p53, as found by a previous study (Li et al. 2002). USP7 over-expression induces programmed cell death (apoptosis) and simultaneously stabilizes p53 by releasing high amounts of the de-ubiquinated form. The USP7 interaction with both ICP0 and EBNA1 may affect cellular functioning by first manipulating the particular protease. This is researched in detail by examining the physical form of USP7 and finding the domains that interact with theses viral proteins and assessing the competition between p53 and EBNA1 for these sites of contact.
One strategy of therapy for cancer cells lacking active p53/containing mutated p53, is t... ... middle of paper ... ...properties of NPM1 are possible reasons why NPM1 also influences cell growth and transformation during tumor development. (Lindstrom, 2010) NPM1 Also interacts with HEXIMI, which regulates RNA Polymerase II transcription. (Lindstrom, 2010) Acetylated NPM1 as well as acetylated histones disrupts nucleosomes leading to transcriptional activation. (Lindstrom, 2010) Acetylated NPM1 is preferentially found in the nucleosomes in association with RNA Polymerase II. (Lindstrom, 2010) The increase in acetylated NPM1 is noted in cancer.
As a result, the vital genetic information contained in these locations goes unread, leading to mutation in the daugh... ... middle of paper ... ...ertions, deletions, and aberrations. Introducing the proper inhibitory factors would force topoisomerase to leave a mutated genome partially degraded, thus blocking the replication of cancerous cells (3). Catalytic topoisomerase inhibitors are a heterogeneous group of compounds that interfere with the binding of DNA and topoisomerase, stabilize noncovalent DNA-topoisomerase complexes, or inhibit ATP binding (9). Most catalytic inhibitors have additional targets and activities that likely contribute to their biological effects. Topoisomerase poisons can be used, along with inhibitors, to induce cellular tumor suppression.
2006). MDM2 functions to keep p53 levels in check during unstressed cellular conditions. However, p53 is stabilized in response to a wide variety of cellular stresses including DNA damage, Radioactive Oxygen Species, hypoxia, oncogene activation, osmotic shock and even ribonucleotide depletion (Vousden and Lu 2002; Han et al. 2008). This stabilization and activation of p53 in response to stress is mediated through many post-translational modifications targeting various domains.
Gene splicing involves removing a fragment of DNA containing the specific DNA sequenc... ... middle of paper ... ...cientist will have to learn how to turn on specific genes when a protein of enzyme is low, and off to avoid too much to ensure the delicate chemical makeup of our bodies is not disrupted. (Blachford, 467) Although there are many risks of gene therapy, the benefits remain to enticing to ignore. Gene therapy poses many risks, but may prove the ideal solution for countless diseases. As seen throughout the past few decades, gene therapy can cure genetically inherited diseases by introducing therapeutic genes into the body. Critics may argue that there are moral and ethical problems associated with this novel technique, but for the most part scientists realize the importance this advancement will have.
Where as Bcl-2/Bcl-xL can bind Beclin 1 and inhibit Beclin 1-dependent autophagic cell death in cancer cells along with suppress p53-dependent and independent cell death. Further studies to elucidate this mechanistic crosstalk are pronounced necessary.
If the damage is extensive then P53 signals that the cell shall undergo apoptosis. If P53 was suppressed and the signals for cell death were inconclusive than that would promote inappropriate cell growth that contributes towards carcinogenesis. In the article COX-2 is an inducible gene that is rapidly induced by inflammatory cytokines that are involved in the protection of cells from the apoptosis process. It is inferred that there is a regulatory role of COX-2 on p53 activity in cancer cells meaning there could be a direct connection and potentially a novel p53-COX-2 pathway. The authors hypothesized that there was a direct correlation of the role of p53 in the regulation of COX-2 expression and the generation of protein and lipid oxidation during the trans-differentiation of MSCs into hepatocyte-like cells.
Additionally, a Cas9 deletion mutant of N. meningitis showed a lowered ability to infect and replicate in human epithelial cells, indicating a strong role for the CRISPR/Cas system in N. meningitis pathogenesis . Therefore, investigating the role of the CRISPR system in down-regulating BLP expression in F. novicida will frame studies on more significant, biologically relevant species. The canonical CRISPR/Cas system has recently been manipulated to edit genes of interest with high specificity in models including human, bacterial, yeast, rodent, and zebrafish cells . With this specificity, CRISPR has solidified itself as a genome editing tool effective for multiple species [ 12-14]. In addition, the need for a crRNA and tracrRNA to be transcribed in vivo has been eliminated by combining the functions into a single, double-stranded, artificial guide RNA (gRNA) .
Many researchers have targeted the CAG repeat as a therapy, or even cure, for the disease. RNA Interference (RNAi): Antisense mediated gene silencing is the post-transcriptional silencing of genes using antisense molecules that are complementary to the base pairs of the targeted mRNA strand (7)(Nielsen and Nielsen, 2013). The antisense molecules supress translation or lead to direct degradation of the targeted strand (7)(Nielsen and Nielsen, 2013). In doing this it decreases the amount of the protein that would have been formed and in the case of HD improves the symptoms (7)(Nielsen and Nielsen, 2013). RNAi is a regulatory mec... ... middle of paper ... ...Conoughey et al., 2010) The main therapies being explored in the search for a treatment for Huntington’s disease involve the use of RNA interference and antisense therapy.
In our knowledge publications that token the advantage of RGD peptide for improving the specificity and efficacy of mda-7 in gene based therapy is limiting (20). Recently Pei et al constructed pCDNA3.1 plasmid expressing RGD-modified mda-7. They created novel RGD motif in the middle of mda-7 backbone by overlapping PCR mutation, then its therapeutic efficacy evaluated in HepG2 cell line. They demonstrated that expression pattern and apoptosis induction of new RGD-IL-24 was similar to IL-24 expression plasmid (20). Theoretically this kind of design may overwhelm true protein folding at the end or disrupt some function although Pei et al didn’t mention it.