Essay On Folding Analysis Of Protein

“Growth factors, also called cytokins, are peptides that transmit within and between cells. They have a major role in the regulation of tissue growth and development” (McCance & Huether, pg. 35).

The research in Dr. Langenfeld’s lab focuses on the genes that regulate lung cancer. The experiment looks closely at the non-small cell lung carcinoma (NSCLC) and immortalized bronchial epithelial cells. Careful study of the carcinoma and epithelial cells has revealed that the mRNA of bone morphogenetic proteins 2 and 4 (BMP-2/4) was highly expressed in the carcinoma. Past studies have shown that BMP-2/4 have certain properties that allow them to activate the differentiation, growth, and migration of cancerous cells in the embryo. After studying these morphogens in lung carcinoma is was revealed that the BMP-2, in its mature state, is significantly more expressed in NSCLC than BMP-4 in cancerous lung tissue, but did not show much effect in normal lung tissue or benign lung tumors. The BMP-2 that was exposed in vitro to the A549 and H7249 human lung cancer lines stimulated significant migration and invasiveness. In vivo trials showed that the growth of tumors of A549 cells in nude mice was highly enhanced. Tumor growth in NSCLC was attempted to be reduced with recombinant through the exposure to noggin or the anti-BMP-2 antibody. Results showed a significant reduction in the tumor growth[1].

Smads are structurally related intracellular signaling mediators, which are activated, among others, by serine/threonine kinase receptors to result in a phosphorylated Smad. The vertebrates found to possess altogether eight Smads (Smad1 to Smad8) with diverse roles in intracellular signaling and they depend for activation on extracellular ligands which bind to receptor extra-cellular domains (Derynck et al., 2003). The different Smads are specific for particular receptors. Smads-2 and -3 are activated through C-terminal phosphorylation by the TβRI and ActRIB, Smads1, -5 and -8 are activated by ALK-1, ALK2, ALK3 and ALK6 in response to BMPs of the TGF- β superfamily. Therefore it can be said that there are Smads that are more specific for TGF-β s and Smads that are BMP-specific. All in all, these five Smads have the common name R-Smads (receptor-Smads) and when activated they form a trimeric complex with a

In addition NDs are so efficient that they can resolve total tumor relapse to the point where they can no longer be detected. To support this standing, two research studies were performed. The first study was done on breast cancer cell lines. In this study antibodies against the epidermal growth factor receptors (EGFRs) were conjugated to fluorescent labeled NDs. This made sure that they are targeting the same position. These EGFR-conjugated NDs then formed a complex with the therapeutic epirubicin. Comparing epirubicin alone with epirubicin that was delivered via the EGFR-targeted NDs showed, that the therapeutic alone lead to an early death of the mice while the ND-delivery lead to the survival of all animals and also to the regression of the tumor. The second research proved, that cancer stem cells (CSCs) can be treat effectively by using ND drug delivery platforms. An example of this finding is the chemoresistance that is often linked to CSCs. The ND-epirubicin complexes can defeat the resistance in the CSCs and kill them. It is not possible to achieve this by using epirubicin alone, this would, as mentioned before, lead to death because of its toxicity. But the ND-epirubicin complexes can effectively

This includes covalent modifications of the p53 gene (altering positive and negative feedback loops in the signaling pathway). P53 gene can be modified at twenty sites, which can change the protein’s behavior in a number of ways. Phosphorylation can inhibit or stimulate protein activity. The attachment or removal of modifying groups controls the behavior of a protein changing it’s activity or stability, which could permit the production of large quantities of the desired protein. Through posttranslational modifications of the p53 gene, this could mediate the control of P53 gene expression through the wnt signaling pathway. The p53 circuit communicates with the Wnt-beta-catenin, IGF-1-AKT, Rb-E2F, p38 MAP kinase, cyclin-cdk, p14/19 ARF pathways. Wnt proteins bind to receptors on the surface of a cell, switching on an intracellular signaling pathway that ultimately leads to the activation of a set of genes that influence cell growth. Wnt transmits its signal by promoting accumulation of free beta-catenin proteins which migrate from the cytoplasm to the nucleus to bind to TCF transcription regulators, creating a complex that activates the transcription of various Wnt-responsive genes, including genes whose products stimulate cell

The purpose of the GFP tag on the gene was to detect the proteins produced by the gene through an anti-GFP antibody. Yeast strains were grown in liquid cultures at either 30°C or 42°C. Proteins were extracted from the yeast strains and amount of total protein in each extract was determined through colorimetric protein assay. An SDS-polyacrylamide gel electrophoresis was conducted. Separated proteins from the gel were transferred to a positively charged nitrocellulose membrane and the blot. Blot was then stained with Ponceau stain to detect total protein. Ponceau stain showed that all lanes contained yeast extract and showed that proteins stayed intact through the experiment. Lastly, primary antibody was added to detect proteins that were bound to the GFP tag in the western blot. After blots were exposed to light, results were obtained on a

IGF-I functions have been shown to be modulated through the interaction of the IGF system and ECM proteins such as fibronectin (FN), vitronectin (VN), collagen (I-IV), laminins, and integrins 15,16. We previously demonstrated that IGF-I interacts with the ECM protein VN through insulin-like growth factor binding proteins (IGFBPs) forming IGF-I:IGFBP:VN trimeric complexes 17. These complexes were shown to induce enhanced cell adhesion, migration and protein synthesis in human keratinocytes 18 and furthermore survival, and anti-apoptosis in both normal and as well as breast cancer cells 19-21. VN has been shown to anchor growth factors in the ECM which in turn enhances cell adhesion and migration of tumour cells 22 and in melanoma, it stimulates cell migration and invasion 23,24 through integrin receptors such as αvβ3 which is over-expressed in metastatic stages 25.

In vitro: Previous study found that AG-370 inhibited PDGF receptor autophosphorylation and the tyrosine phosphorylation of intracellular protein substrates that coprecipitated with the PDGF receptor in digitonin-permeabilized

There are all kinds of tumor markers of colon cancer, the classification is different. Some classic markers such as CA242, CA199, CA72-4, and CEA have been applied to clinical studies, and Some classic markers ,such as TGF,have the potential to serve as markers for colon cancer Clinical application.

and two β chains, which make it structurally similar to the type 1 insulin-like growth factor

DNA can be experimentally manipulated in cells in order to highlight the effects of certain protein functions. Overexpression of podocalyxin was induced in the DNA which means that the production of this cell membrane protein was increased. Having done this, Graves et at. were able to compare normal breast cancer cells (wild-type) to breast cancer cells that overexpressed podocalyxin. Movement of breast cancer cells results in the formation of small

We examined the viability of the cells in response to the chemotherapeutic as a function of the matrix stiffness (Figure 2C). We observed that as the cells underwent apoptosis they detached from the substrates. Consequently, we collected the media before (Day 7) and after (Day 10) the chemotherapy to quantify the number of cells in suspension. As depicted on Figure 2C, the PC cells cultured on softer substrates experience larger increase in dead cells resulting from the chemotherapy compared to the PC cells growing on stiffer substrates. As Figure 2A shows, both Gemcitabine concentrations lead to a change in cell morphology and a higher decrease in cell area on the softer PC tumors (3kPa and 8kPa) compared to the stiffer PC tumors (25kPa and control group).

Campbell and Farrell define proteins as polymers of amino acids that have been covalently joined through peptide bonds to form amino acid chains (61). A short amino acid chain comprising of thirty amino acids forms a peptide, and a longer chain of amino acids forms a polypeptide or a protein. Each of the amino acids making up a protein, has a fundamental design that comprises of a central carbon or alpha carbon that is bonded to a hydrogen element, an amino grouping, a carboxyl grouping, and a unique side chain or the R-group (Campbell and Farrell 61).

A co-expression study was undertaken to evaluate the correlated expression of MDM2 and VEGF, finding that, over eight different cancer cell lines, higher MDM2 expression meant higher VEGF mRNA, with the cell lines with lost

PEG-MGF (PEGylated Mechano Growth Factor) is an analogue of the insulin-like growth factor (IGF-1). It initiates the division of myoblasts and enables the fusing and maturation of muscle fibers, a process that is crucial in the growth of adult muscle. The variation between MGF and IGF-1 is as a result of the MGF property to stimulate division of myoblasts by stimulating a set of different receptors. The synthetic MGF (PEG-MGF) peptide is water soluble and after intramuscularly administration it ends up in the bloodstream. On the other hand, natural MGF is locally synthesized and does not get into the bloodstream. MGF has a very short stability period as it breaks down rapidly once introduced in the body and hence the synthetic peptide is PEGylated to ensure it is not broken down when in the bloodstream hence retaining its bioactivity and efficiency. PEGylation is the joining of a Polyethylene glycol (PEG) structure with a larger molecule. As such, the PEG serves as a protective coating to the MGF molecule. PEG-MGF is therefore a combination of Polythylene glycol and MGF (Mechano Growth Factor). The molecular mass for PEG-MGF is 2867.2 and its molecular formula is C121H200N42O39. The molecular sequence of PEG-MGF is PEG-Tyr-Gln-Pro-Pro-Ser-Thr-Asn-Lys-Asn-Thr-Lys-Ser-Gln-Arg-Arg-Lys-Gly-Ser-Thr-Phe-Glu-Glu-Arg-Lys-NH2. PEGylated MGF has a relatively higher bioavailability and has an extended half-life.