Alteration of p53, p53 Family Proteins and Their Isoforms by H Pyroli in Gastric Cancer

Its locus is particularly amplified in these noted tumours leading to the progression of these cancers, it can be suppressed by p53 (tumour/ proliferation suppressor) which represses the EZH2 promoter, resulting inhibition of cell proliferation and invasion (Bracken, 2003; Xiao, 2011).

The purpose of this research was to determine the mechanisms in naked mole-rats that restricts cell proliferation and tumor formation. Contact inhibition is a mechanism observed where cell proliferation stops when two cells come in contact with one another. This process is caused by elevated levels of p27 cyclin-dependent kinase inhibitor which stops cells in the G1 phase from dividing. The cylcin-dependent kinase inhibitor p16 is also thought to regulate contact inhibition but its levels do not change in mice or human samples. Tumor-suppressor genes Rb and p53 are present in high concentration during contact inhibition to help control cell proliferation and apoptosis respectively. It was hypothesized that the naked mole-rats' cancer resistivity

TP53 is a 20kb long gene located on the small arm of chromosome 17 [18]. It is the first tumor suppressor gene to be identified and the most extensively studied [19, 20]. First described in 1979, this gene was first believed to be an oncogene, a cell growth promoter [19]. However, data form in-vivo studies performed years later provided convincing evidence supporting its tumor suppressive activity [18, 21].

Mutations (for most cancers) must appear in both tumour suppressing genes and oncogenes for cancers to form. The tumour suppressing genes and oncogenes act in complementary fashion to one another; one pulls forward, and the other pushes back ensuring that the cell cycle occurs in a controlled manner (Sherr, 2004).

Besides inducing apoptosis and controlling the cell cycle, p53 has been demonstrated to be a central component and key regulator of the metabolic stress machinery. The metabolic balance between glycolysis and oxidative phosphorylation is heavily coordinated by p53 activity, which is activated by

Histone acetylation is regulated by two covalent modifying enzymes, acetylases and deacetylases, and plays a key role in gene expression of eukaryotes. It has been revealed that histone deacetylase (HDAC), which is overexpressed in several tumor cells. plays a critical role in carcinogenesis. Moreover, plenty of studies have showed that the expression of tumor suppressors including p53, p21, and gelsolin, are repressed, whereas, tumor activators including hypoxia-induced factor-1 and vascular endothelial growth factor, are up-regulated in HDAC-overexpressed cells.

Transformation-Related Protein 53, also known as TP53, is a tumor suppressor gene. It is named after its molecular mass. The gene was discovered by Arnold Levine, David Lane, and William Old in 1979 and was voted molecule of the year by science magazine in 1993. Although, it was not until 1989 that it was revealed to be a tumor suppressor gene. It was previously thought of as an oncogene. TP53 encodes for a protein, called p53 protein, that helps to regulate the cell cycle and inhibits mutations in the genome as well. Both of these functions help to conserve stability. One of the reasons for TP53’s high importance, and the extensive research on the gene, is its function to suppress cancer cells in multicellular organisms, including humans (Vijayaraj).

The central DNA binding domain is the most highly conserved region of p53, when compared to its other family members, p63 and p73. Loss of tumor suppressor function of p53, as seen in most cancers, results from missense mutations in the DNA

Functional studies have demonstrated that combination of primary BRAF or NRAS driver genes together with additional genetic alterations such as deletion of CDKN2A or PTEN and inactivation of tumor protein p53 (TP53) tumor suppressor gene as a necessary event to bypass OIS79–82. High frequency BRAF mutation in concert with loss of function in tumor suppressors (PTEN, p53) and cell-cycle control genes (CDKN2A) has also been observed in ~40% human melanoma and most melanoma cell lines further highlighting the importance of co-operating pathways to fully form

In the spot assay, p53 mutant T155N was tested for binding by the color it develops. On the high adenine agar plate, the p53 strains, wild type (wt), mutant T155N (mut), and deletion (del), produced white cultures with all p53 response element (RE) sites, consensus (con), p21, and BAX. Therefore, all p53 strains showed transactivation because there was already enough ADE2 protein on the plate (see Figure 1B). Unlike the high adenine agar plate, the low adenine agar plate showed significant differences between the p53 strains and the p53 REs. The p53 wt strain developed white cultures while the p53 deletion strain developed red cultures. The p53 mut strain developed a pink culture with p53 RE con and red cultures with p53 RE p21 and BAX. In this case, p53 wt shows transactivation and a high binding affinity with all three p53 REs. Contrarily, the p53 del strain shows no transactivation and binding affinity with all the p53

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

Cancer is a difficult disease to combat in any organism. Whether cancer comes through a carcinogen, virus, bacteria, or genetic history the process is the same for most cancers. DNA is damaged in a cell and stops the process of apoptosis and the cell divides uncontrollably. Eventually the cells become a tumor and reach the bloodstream spreading through metastasis. In response to this many organisms have a defense to help control and destroy these cells through a protein called p53. This protein is coded for by the gene Tumor Protein 53 or TP53 and helps to control the cells ability to divide rapidly. This gene can be found in small organisms like mice to large mammals like elephants and whales. Cancer’s success is dependent on a mutation in

. The TP53 gene is located on the short (p) arm of chromosome 17 at position 13.1. [7]. TP53 has many important mechanisms of anticancer function and plays a role in apoptosis, genomic stability, and inhibition of angiogenesis. In its anti-cancer role, p53 works through several mechanisms: p53 can activate DNA, and repair proteins when DNA has sustained damage. Thus, it may be an important factor in aging. The gene has a very important location in the nucleus of our cells, where it binds directly to DNA. TP53 can arrest growth by holding the cell cycle at the G1/S regulation point on DNA damage recognition. If it holds the cell here for long enough, the DNA repair proteins will have time to fix the damage and the cell will be allowed to

Stomach Cancer is cancer of the stomach which is also known as Gastric Cancer. It is a disease where malignant cells arise from the lining of the stomach which could eventually grow into a tumor found in the upper part of the abdomen and just below the ribs. Since the stomach is a part of the body’s digestive system, it produces acids and enzymes that break down food before passing through the small intestine which can cause the cancer to develop in any part of the stomach and spreads up towards the esophagus. The cancer happens over a period of a few years of bad acids being ate or inhaled which causes inflammation in your gut called gastritis, long-lasting anemia that continues to grow in the stomach that can also put you at a higher risk to get cancer. Although, not knowing exactly what makes stomach cancer cells, smoking, being overweight, exposure to coal, metal, timber industries all put you at a higher risk of receiving the cancer.

It may be possible to correct an abnormality in a tumor suppressor gene such as P53 by inserting a copy of the wild-type gene; in fact, insertion of the wild-type P53 gene into P53-deficient tumor cells has been shown to result in the death of tumor cells (3). This has significant implications, since P53 alterations are the most common genetic abnormalities in human cancers. The over expression of an oncogene such as K-RAS can be blocked at the genetic level by integration of an antisense gene whose transcript binds specifically to the oncogene RNA, disabling its capacity to produce protein. Experiments in vitro and in vivo have demonstrated that when an antisense K-RAS vector is integrated into lung cancer cells that over express K-RAS their tumorigenicity is decreased (4).