Tp53 Essay

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

When this checkpoint is passed, cdk4 and cyclin D interact. This interaction results in phosphorylation of the retinoblastoma protein, which in turn allows activation of the transcription factor E2F. Active E2F promotes expression of the cyclin E gene. Cyclin E (protein) and cdk 2 interact to

(#2) CDKN1A is a protein coding gene. The purpose CDKN1A serves in the cell is that it works as cell cycle regulator at the G1 checkpoint and is responsible for the cell cycle arrest at that checkpoint. CDKN1A encodes a potential cyclin-dependent kinase (CDK) inhibitor which then prevents the phosphorylation of critical CDK substrates and blocks cell cycle progression, thus functioning as a cell cycle regulator at the G1 checkpoint. CDKN1A, along with p53, are both involved

The gene most associated with HCC is the TP53 gene, which is a tumor suppressor gene universal among many cancers. The p53 protein, when turned off, can mistakenly cause cancer since they are normally turned on (Rhine 4). When normal, the TP53 gene assures that cells do not grow beyond where the should, meaning they have anchorage dependence and density dependent inhibition. When damaged, abnormal cells and the formation of HCC can occur since the P53 protein is involved in cell cycle functions and apoptosis, because it does not stop the cells from accumulating mutations over time if its function is degraded (¨“Do We Know [...]?¨, Debuire and Lemoine). This tumor suppressor gene follows Mendelian rules, meaning they are recessive and must

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.

Additionally, p16 has been explained in the cytoplasm of some tumor cells where roles other than proliferation control might occur (24). Considering the data collected on the subject, it has been hypothesized that a function of p16 is a universal cancer suppressor, working to block numerous pro-neoplastic cell capabilities like invasion, proliferation, and angiogenesis. The p16 gene appears to be more than just a cell cycle progression regulator. Additional studies are needed to increase our understanding of its potential job in the progression of cancer and the development of cancer

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

Chemotherapy encompasses the use of chemical agents to stop the growth and eliminate cancer cells even at distant sites from the origin of primary tumor. Cisplatin, cis-diamminedichloro platinum (CP), with the molecular formula cis-[Pt(NH3)2Cl2], is one of the most remarkable platinum-based drugs used in the battle on cancer 1-3.Its cytotoxic mode of action is mediated by its interaction with DNA to form DNA adducts, primarily intrastrand crosslink adducts, which activate several signal transduction pathways, including those involving ATR, p53, p73, and MAPK, and culminate in the activation of apoptosis. DNA damage-mediated apoptotic signals, however, can be attenuated, and the resistance that ensues is a major limitation of CP based chemotherapy. The mechanisms responsible for CP resistance are several, and contribute to the multifactorial nature of the problem. CP is an important anticancer drug used for the treatment of cervical, testicular, ovarian, head and neck and non-small cell lung carcinoma and many other types of cancer in the globe 4.

Cell death relates to brain diseases which can be organized by the loss of neurons. Caspases are also involved in Huntington’s disease which is the result of a mutation in the huntingtin protein. “Several human papilloma viruses or (HPV) have been implicated in the causing of cervical cancer. One of them produces a protein that binds and inactivates the apoptosis promoter”(Source 2) “Cancer is an example where the normal mechanisms of cell cycle regulation are dysfunctional”(Source 6).Many cancer cells could secrete different molecules that could completely avoid apoptosis. “Increased apoptosis in diseased cells is a characteristic of AIDs, Alzheimer’s and Parkinson's disease”(Source 6). “There is a variety of molecular mechanisms that tumor cells use to suppress apoptosis”(Source 6). Viruses coming from many different families stop apoptosis of

Due to its potent tumor suppressive activity, a molecular understanding of p53 action will create significant experiences into specific procedures that limit tumor growth and may identify key

Tumor suppressor genes in normal cells act as braking signals during phase G1 of the cell cycle, or to stop or slow the cell cycle before S phase. If tumor-suppressor genes are mutated, the normal brake mechanism will be disabled, resulting in uncontrolled growth. Mutations in tumor-suppressor genes cause loss-of-function. Loss-of-function mutations generally only show up when both copies of the gene are mutated. In other words, if a pair of tumor suppressor genes are lost or mutated, their functional absence might allow cancer to develop. For instance, a growth factor receptor may send signals even when

Through the study, they did in fact find that while humans have 1 TP53 gene, African elephants have 19 different cancer suppressor genes. These genes were brought about through generations of evolution within the elephant community. It can be said that elephant cells demonstrated increased apoptotic response following DNA damage compared to human cells.

This begs the question upon how the DEK protein is able accomplish this task, by evaluating the biological pathways that DEK utilizes. The most commonly inactivated tumor suppressor gene, is the human p53 protein. Despite this, the protein has a short half-life and undergoes continual proteolytic degradation in healthy cells, regulated by the E3 ligase MDM2 [31]. MDM2 works by physically up taking the trans activation domain of the p53 and will thereby prevent its transcriptional production [32]. However, the feedback loop of the MDM2- p53 complex can be disturbed by stress due to DNA damage or lack of oxygen leading to cell death [30]. Bax, is a cell death inducing factor that belongs to the Bcl-2 family. Under regular conditions it forms in the cytosol and adheres to the membrane. Once the cell has been signaled for apoptosis, Bax will translocate into the mitochondria where it will become an integral protein of the membrane. Cross-linking Bax proteins will initiate for the expulsion of apoptotic factors from the mitochondria in order to initiate the apoptotic pathway [35-38]. Next, these

Several pieces of evidence suggested that the ability to bypass senescence is the main molecular mechanism involved in the progression of pre-malignant to malignant cells (Braig 2005; Collado 2007). This hypothesis is based on the concept of oncogene-induced senescence, which was established after demonstration of p53- and p16Ink4a - mediated senescent-like arrest in response to expression of oncogenic Ras in normal primary cells (Collado 2007). This event (OIS) has been considered as highly possible mechanism to prevent proliferation of incipient cancer cells (Sinha 2015). Consistent with this concept, senescent cells have been shown in a number of different benign lesions, including

In addition, several tumor suppressor genes are frequently altered in PDAC. The most mutated one is p53 which is inactivated in 75%. (15) P53 has a vital role in regulating cellular stress and determines cell fate by inducing programmed cell death in response to DNA damage. (14) Studies revealed that mutations in p53 results in accumulation of the mutant protein within the cell nucleus and decrease tumor’s sensitivity of chemotherapy as a result of losing its apoptotic function. (16) SMAD4 is another tumor suppressor gene which is mutated in around 55% of the tumor. (14) Inactivation of SMAD4 leads to the loss of a significant part of cell growth suppression. (16) The third essential tumor suppressor gene is CDKN2A that is altered in 26% of the tumor. (17) CDKN2A control cell cycle and when it is silenced it increase tumor size the likelihood of metastases. (14,16)