Of The Mouse Arf Tumor Suppressor?

Cancer Institute is the 1st of the 3 cancer institutes. For more than a whole

Mice play one of the main roles in predators ,plants and everything else it interacts .The mice can affect organisms around its ecosystem. Mice are small little organisms.Its Ecosystem is in grasslands,and many burrows onto the ground.They can sometimes play as the ´parasite´ to the ones it invades homes,for its considered an invasive species.They are part of the food web.They eat little nuts,plants and grains it finds.But it's an omnivore so it is capable to consume meat.They affect those around and interacts with the organisms,For they are Important.

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).

Scientists from George Washington University medical center have found a missing link in mitosis that brings hope for cancer researchers. They have found a protein known as Arpc 1b that is an activator for an enzyme called Aurora A that is important in early stages of cellular reproduction. Cells divide and separate poles to create new cells. If all goes well two new cells are produced, but in some cases the protein is over used, and abnormal cells are produced which lead to cancer. Pharmaceutical industries are targeting Aurora A and trying to prevent it. This is the next step to help scientists find a way to stop the activity of Arpc in cancer cells. As an example, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious or life-threatening medical conditions. They are among the worlds leading biotech companies, with multiple products on the market and a promising development pipeline. At Genentech, James Sabry, M.D., Ph.D. who is the Vice President, said, “If we understand basic science, our drugs make it to market. If we don’t, the company dies.” Roche, Genentech’s parent company, spends more on research and development than any country in the world ($9.5 billion annually). Understanding cell development and cell division help the

P53 is a tumor suppressor gene. In all kinds of malignant tumors, above 50% appears p53 gene mutation. The protein encoded by this gene is a transcriptional factor, which controls to start the cell cycle. Many signals of the cell health directly send to the p53 protein. It also decides when the cells begin the division. If the cells are damaged and cannot be repaired, the p53 protein would start the boot process and lead the cell go to apoptosis died. Some p53 deficient cells without this control, under adverse conditions, cells will continue to split. Just like any other tumor suppressor, p53 gene normally plays the role of slowing down or monitoring the cell division. The Inhibiting cancer genes “p53” in cells judges the extent of DNA damage.

. 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

Telomeres are the repeating end caps of chromosomes. As a cell divides and duplicates, the telomere genes began to shorten. The shortening of the genetic end caps is considered a biological clock which counts down to a cellular death, also known as apoptosis. Aging is accompanied by telomere shortening and it has been discovered in age related diseases, such as premature aging syndromes. The consequences of a telomere dysfunction are very diverse and can include nail dystrophy, abnormalities in skin pigmentation, aplastic anemia, pulmonary fibrosis, and a rapidly expanding list of other diseases. The erosion of the telomere genes is meant to suppress malignant transformations. In exceptional cases, it can cause chromosomal instability and promote the formation of tumors. Telomerase is the enzyme which can replace telomere genes lost through cellular senescence. Unregulated expression of telomerase has been seen in a majority of cancers. Telomerase is a double edged sword as it allows cancerous cells to divide without regulation. The accumulated evidence on telomere genes would suggest that they have the ability to maintain telomere length and to mask them from recognition as damaged DNA. Understanding telomerase regulation and telomere length maintenance will uncover many mysteries in the control of aging and

Androgens depletion, known as androgen ablation therapies, are the first line treatment for prostate cancer, targeting feedback receptors in the hypothalamus and AR in the tumour cells.10 However, often there is high change of relapse and it could be due to multiple factors. Firstly, not all prostate carcinomas express AR, as sometimes the gene is silence by promoter hypermethylation.11 It is thought the growth and survival signals of these tumours are due to peptide growth factors. Additionally, various peptide growth factors and cytokines can activate AR synergistically with or without steroid ligand. Examples are fibroblast growth factor 7 (FGF7), epidermal growth factor (EGF), and interleukin-6 (IL-6). 9 Furthermore, prostate cancer cells under androgen depletion which may amplify AR gene leading to increased sensitivity towards minimal levels of androgens and other signalling proteins. 12 Alongside, there are numerous co-activator proteins that mediate the AR on the chromatin structure and transcriptional initiation via other signalling pathways.9 With these factors being into play, androgen ablation does not induce apoptosis in androgen- independent cell, and thus having no suppression in the rate of their growth. 13

Aim 1: Investigate the post-transcriptional mechanism underlying MALAT1’s role in SRSF1/p53-mediated OIS in HNCC cells. All in vitro experiments performed in this Aim will utilize three cell lines: normal (control) cells, MALAT1-overexpressed (MALAT1+) HNCC cells and MALAT1 knocked down (MALAT1-) HNCC cells via antisense oligonucleotide (ASO) therapy. 1A. To determine if

MALAT1 co-localizes to nuclear speckles with SRSF1 and has been shown to regulate AS by modulating cellular levels of SRSF1 phosphorylation. SRSF1 binding sites have also been found at the 5’ end of both human and mouse MALAT1. Interestingly, we have shown that the RNA-recognition motif 2 (RRM2) of SRSF1 interacts with the RS domain and that this interaction facilitates the proper directional phosphorylation mechanism seen for proper SRSF1 nuclear translocation. Scientific literature and empirical evidence regarding the relationships between SRSF1, p53/OIS, and MALAT1 have led us to our central hypothesis that MALAT1 overexpression disrupts the interaction between the RRM2 and RS domain in SRSF1, subsequently impairing its phosphorylation and thus its nuclear translocation. This change in subcellular localization, in turn, destabilizes p53, leading to loss of OIS in cervical cancer cells. We will address this hypothesis in the following Specific Aims:

Cancer is a disease of the cell cycle. Some of the body’s cells divide uncontrollably and tumors form.

The transcription factor NF-κB is recognized to regulate a notable number of cellular signaling pathways, which are related to cancer. During carcinogenesis, NF-κB targets a number of cytokines, pro-inflammatory molecules, growth factors, cell adhesion molecules, oncogenes, also pro/anti-apoptotic proteins. NFkB is a ubiquitously expressed eukaryotic transcription factor that is answerable for the regulation of numerous genes. Five subunits have determined for NFkB: p50 (NFkB1), p52 (NFkB2), p55 (RelB), p65 (RelA), and c-Rel (Rel). When NFkB is activated by inducements such as bacterial lipopolysaccharides (LPS) or pro-inflammatory cytokines, it displaces to the cell nucleus and starts the expression of a variety of target genes, such as Tumor

In the year 2016, the American Cancer Society projected that 595,690 individuals will pass due to cancer and 1,685,210 individuals will develop a new cancer case. Many scientists such as Dr. Bert Vogelstein or Dr. Robert Weinburg have been trying to understand the mechanism behind cancer and create therapeutic agents that could potentially prevent this disease from occurring. The most novel and studied gene and protein in regards to cancer is p53. The protein was discovered in the 1970s when research was focused on cancers that are caused by viruses and was later identified as being a tumor suppressor (1). One of the most studied areas of cancer is how p53 functions and its role in the cell cycle which has led to studies that target p53 as a therapeutic agent for cancer (1). In the year 2001, it was found that the protein product of the gene hSIR2SIRT1, which is a homolog of S. cerevisiae Sir2 protein, deacetylates the p53 protein and allows for either cell growth arrest or apoptosis (2). Due to this finding, the Sirtuin 1 protein has been heavily studied and even been targeted as being a therapeutic target for varying diseases and even involved in the phenomena known as caloric restriction (3–5). ¬

The p53 is a vital tumour suppressor protein in humans which is important for cell cycle regulation. Ablation of the p53 protein causes the cell to proliferate infinitely that contributes to the development of tumours. Through the cell-autonomous program the cell-cycle arrest and apoptosis is caused by the presence of p53. The aim of the journal is to study cellular senescence program in hepatic stellate cells that is p53-dependent which is formed by dying hepatocytes which secret factors that influence the tissue microenvironment, preventing fibrosis, cirrhosis and liver cancer via promoting p53 senescent in these HSCs. The research objectives explain that fibrosis is limited through the p53-mediated senescence program by stopping HSC proliferation through cell-autonomous canonical senescence regulators and the non-cell-autonomous effects of SASP on ECM and immune surveillance. Currently there is a debate on the role p53 plays in HSCs which influences later stages of liver cancer and the research exhibits that through non-cell-autonomous mechanisms, p53 can inhibit cancer by manipulating the tissue microenvironment.

Tumor suppressor genes encode proteins, inhibiting excessive cell proliferation and division, through protein inhibitors for cell cycle progression or promoting differentiation and apoptosis via proteins that involved in induction of apoptosis. Mutations that cause inactivation or loss of function in these tumor suppressor genes, result in inactivation of P53, pRb, PTEN, NF1/NF2. The mutations can be deletion or insertion, nonsense or missense mutations, frame shift mutations, or epigenetic tuning events such as methylation, which lead to neoplasia. These mutations are recessive and clinically important, only when they appear as homozygous or a combination with heterozygous alteration. The