Protein : The Normal Function Of The Target

Proteins are the metabolic workhorses of the cell; they engage in a variety of essential activities ranging from enzymatically catabolizing macromolecular food sources to serving as structural components that maintain cell stability. Maximizing protein function relies on intricate non-covalent interactions occurring on the secondary, tertiary, and quaternary levels that help determine the overall shape of the protein. In their native states, proteins will assume the most energetically favorable configuration. Occasionally however, cells are exposed to exogenous disruptions such as heat stress. Heat Stress can compromise protein three-dimensional structure. Hydrophobic residues tend to be buried in the interior of the protein but when

A protein has multiple existing structures, these are the primary, secondary, tertiary and quaternary structures which occur progressively. A protein is essentially a sequence of amino acids which are bonded adjacently, and interact with one another in various ways depending on the R group that the amino acid contains. There are 20 different amino acids which are able to be arranged in any given order, thus giving rise to a potential 2.433x1018 (4.s.f) different combinations, and therefore interactions between the various amino acids.

Epithelial-mesenchymal transition (EMT) is a cellular process that is essential for normal processes in many organisms, including embryonic development and wound healing, and is recapitulated in human disease, contributing to organ fibrosis and cancer progression (Thiery et al. 2009; Yang and Weinberg 2008). EMT describes the conversion of a cell with an epithelial phenotype to one with mesenchymal characteristics and can be a partial or complete transformation. Epithelial cells form the borders of tissues and organs, and are characterized by apical-basal polarity, contact with a basement membrane, and strong adherence to other epithelial cells through intercellular junctions including adherens junctions, tight junctions, and desmosomes. Conversely, mesenchymal cells have front-rear polarity and generally lack cell-cell contact, allowing them to be motile. During human embryonic development, EMT is essential for the formation of a variety of tissues, including mesoderm, neural crest, somites, palate, pancreas, liver, reproductive tracts, and heart valves (Thiery et al. 2009; Yang and Weinberg 2008). After development, partial EMT also contributes to wound healing (Thiery et al. 2009). However, EMT can also play a more insidious role by factoring into tumour progression.

Figure 2 [3]: The role of cadherin and catenin in the binding of cancer cells to the endothelium.

Proteins are primarily considered to have one primary function to serve its role in an organism, however studies have observed to have multiple functioning proteins known as moonlighting proteins (Khan et al. 2014). Moonlighting proteins along with primary functions, have secondary functions that are not related to the primary function and does not correlate to the primary or other functions (Khan et al. 2014). The multifunctional proteins play essential roles in carrying out biochemical functions which aids in the cell growth but are not caused by gene fusion and multiple RNA splice variants (Amblee et al. 2015). The discovery of moonlighting proteins was first discovered by Piatigorsky and Wistow while observing crystallins (Khan et al. 2014). Crystallins, are structural proteins that are found in the eye lens that exhibit enzymatic activity to make the lens itself (Khan et al. 2014). Crystallin has a primary function to help form the lens of the eye by acting as a structural protein (Amblee et al. 2015). Besides enzymatic activity, crystallin was observed in other mammals to have secondary functions such as metabolic functions which are helpful in prokaryotic (Khan et al 2014). Most moonlighting proteins are characterized as cytosolic enzymes and chaperons, or in other words helping proteins (Amblee et al 2015). The multifunctional proteins or moonlighting proteins can also be identified as receptors, channel proteins and ribosomal proteins (Khan et al. 2014). Due to the

Proto-oncogenes are genes that code for cell division enhancing proteins or proteins that prevent typical death in a cell. When these genes become mutated, they are called oncogenes. The cell division stimulating proteins that proto-oncogenes create work in a signal transduction cascade. The signal transduction cascade is the set of steps through which a receptor in the membrane receives the signal, which is a growth factor in this case, and activates different proteins and factors, leading to the transcription factor (a protein that binds to DNA to affect the transcription of a gene) being activated and entering the nucleus. In the case of proto-oncogenes, the signal transduction cascade leads to cell division. Proto-oncogenes can become oncogenes when a proto-oncogene is mutated, the genes are rearranged, or the number of proto-oncogene copies increases. The

Cervical cancer is the leading cause of cancerous death, in women, since 1950. Approximately 200,000 cervical cancer patients die each year in developing countries. Strains like HPV 16 and 18 cause about 70% of cervical cancer in women– one of the top causes of death in the world (WebMD, 2010, p.1). In the Unites States, about 10,000 women acquire the disease and 3,700 die annually Human Papilloma Virus (HPV) is directly associated as a cause of cervical cancer. This virus affects the skin and genital area and, in some cases, it can also infect the throat and mouth. Since the HPV is passed from one person to another through skin-to-skin or sexual contact, sexually active people are more prone to this virus. Merck

Proteins are polymeric chains that are built from monomers called amino acids. All structural and functional properties of proteins derive from the chemical properties of the polypeptide chain. There are four levels of protein structural organization: primary, secondary, tertiary, and quaternary. Primary structure is defined as the linear sequence of amino acids in a polypeptide chain. The secondary structure refers to certain regular geometric figures of the chain. Tertiary structure results from long-range contacts within the chain. The quaternary structure is the organization of protein subunits, or two or more independent polypeptide chains.

The Functions of Proteins Introduction Protein accounts for about three-fourths of the dry matter in human tissues other than fat and bone. It is a major structural component of hair, skin, nails, connective tissues, and body organs. It is required for practically every essential function in the body. Proteins are made from the following elements; carbon, hydrogen, oxygen, nitrogen and often sulphur and phosphorus.

If the APC protein were to experience a nonsense mutation, the most common mutation in regards to this specific genetic disease, the destruction complex would not perform correctly and the wnt-signaling pathway would be stimulated. Problems begin to arise when “the Wnt/Beta-catenin pathway is activated [by] a Wnt ligand [binding] to seven-pass transmembrane Frizzled receptor and its co-receptor, low-density lipoprotein related protein 6 (LRP6) or its close relative LRP5” (MacDonald, et. al 2009). Once the wnt-signaling pathway is stimulated, a Wnt-Fz-LRP6 complex forms and takes in the Dishevelled (Dvl) protein, resulting in the phosphorylation and activation of the recruitment of the axin complex, destruction complex, to the receptors. (MacDonald, et al 2009). Due to the phosphorylation within the Wnt-Fz-LRP6 complex, the axin complex is not able to phosphorylate Beta-Catenin, which leads to the excessive accumulation of the protein in the cytoplasm. Researchers witnessed the development of numerous intestinal adenomas in transgenic mice with stabilized mutant Beta-catenin, therefore the results suggest that dysregulation of Beta-catenin is a key oncogenic event that follows the loss of APC function. (Tarapore, et. al 2011). The loss of the destruction complex’s normal activities results in elevated levels of Beta-catenin and downstream effectors such as CCND1,

The macromolecule protein is made up of monomers called amino acids which are nitrogen-containing molecules (Hoffman and Falvo, 2004). These amino acids are joined together by peptide bonds. Amino acids can be categorized into three types called essential amino acids, semi-essential amino acids and non-essential amino acids. Essential amino acids (e.g.: valine and phenylalanine) refer to amino acids that are not synthesized in the human body; hence it has to be provided in the diet. Semi- essential amino acids represent amino acids that are synthesized in the body but not in adequate amounts; therefore it has to be supplied by the diet in small amounts. Non- essential amino acids (e.g.: alanine and glycine) are synthesized by the body and

Immunoblot analysis showed that GSK-3β knockdown caused significantly enhanced the level of β-catenin that activate the Wnt pathway, while BPA treatment decreased the level of β-catenin that enhanced due to GSK-3β knockdown group (Figure 10G-H). Furthermore, the level of downstream target genes of Wnt/β-catenin pathway such as cyclinD1 and survivin after GSK-3β knockdown enhanced but BPA treatment caused decreased their levels that enhanced due to GSK-3β knockdown (Figure

In the absence of Wnt, cytoplasmic β-catenin protein is constantly degraded by the action of the Axin complex. β-catenin protein binds to the Axin complex where is phosphorylated by CK1 and GSK3 and this results in its proteasomal degradation and prevents it from reaching the nucleus to activate Wnt target gene expression (He et al., 2004). The Wnt/β-Catenin pathway is activated when a Wnt ligand binds to the receptors Frizzled (Fz) and LRP5/6 (low-density lipoprotein receptor-related protein 5/6) The formation of a likely Wnt-Fz-LRP6 complex, together with the recruitment of the protein Dishevelled (Dvl), results in β-catenin phosphorylation and stabilization, which then, accumulates and travels to the nucleus to activates Wnt target gene expression (Figure 1b) (MacDonald et al.,

PM331 Essay: Exosomes, their cell biology, normal function in the cell, and role in disease.

β-catenin is a proto-oncogene and it is encoded by CTNNB1 gene. It forms a component of the E-cadherin – catenin unit which plays essential roles in the cell differentiation and maintenance of the normal tissue architecture. Also, it involves in the signal transduction, the canonical WNT signalling pathways (β-catenin dependent WNT signalling pathways). The activated canonical WNT signalling pathways increase the level of β-catenin in the cytoplasm, causing translocation of β-catenin into the nucleus. This raises the level of β-catenin in the nucleus, leading to the initiation of the transcriptional activation through the LEF/Tcf pathway. The process involves in the canonical WNT signalling pathways is important in cell proliferation. The deactivated canonical WNT signalling pathways will casue β-catenin to undergo ubiquitination and proteosomal degradation through the β-TrCP/Skp pathway. These processes happen under normal circumstances of functional β-catenin.