The protein kinases that are known to target this transcriptional activation domain of p53 can be roughly divided into two groups. However, further studies on expression levels of Bcl-2 on prognosis of cancer are still being investigated.
Most of these mutations destroy the ability of the protein to bind to its target DNA sequences, and thus prevents transcriptional activation of these genes.
However, further studies must be done to determine if all of the significant germline p53 mutations provide the same risk for cancer development 3. By changing the residues, the protein will not be able to function properly as a tumor suppressor.
Some studies have shown that germline p53 mutation have been seen in patients with cancer. The protein structure as a whole is very disordered and relies on other proteins for stability.
Most human cancers bear p53 gene mutations. In their first model, the p53 response to low stress results in cell cycle arrest, growth inhibition, DNA repair, which enables cells to restore the damage induced by the cellular stress.
Nucleophiles will readily attack causing the stabilization of the DNA binding site. Human cancers such as those found in the stomach and colon; have altered expression of Bcl It then affects DNA binding, which causes the cell to divide unnaturally and form tumors.
The observation of specific deletions in human tumors is another example of research that suggested the involvement of tumor suppressor genes in the development of human cancers.
Today, cancer has become one of the leading causes of death worldwide. In their second model, when the cells receive high stress that cannot be restored, p53 acts as a killer that can induce apoptosis or senescence, preventing proliferation of defective cells.
Another region of tumor suppression exists in the proline-rich region. The p53 apoptosis and senescence are the main mechanisms that are responsible for its tumor suppression.
Activated p53 transcribes MDM-2 which is a major negative regulator of p53 in the cell. Rainwater and colleagues tried replacing cysteine with serine. The p21 gene contains several p53 response elements that mediate direct binding of the p53 protein, resulting in transcriptional activation of the gene encoding the p21 protein.
All of these residues happen to be located in the DNA binding domain 1. This mechanism, in synergy with the inactivation of the cell cycle regulator pRb by the HPV protein E7, allows for repeated cell division manifested clinically as warts.
When p53 becomes stabilized and activated in hESCs, it increases p21 to establish a longer G1. Further experimental studies obtained in vitro and in vivo have indicated that wild-type p53 protein can suppress the transformed phenotype of several types of cancer in humans by inducing different biological effects including maintenance of genomic stability, inhibition of abnormal cell proliferation and differentiation, and induction of apoptosis.
Also, p53 acts as a transcription factor for PUMA 7.
Rainwater and colleagues tried replacing cysteine with serine. Thus, it may be an important factor in aging. In unstressed cells, p53 levels are kept low through a continuous degradation of p In cellular and molecular research, p53 is highlighted to be a specific point of focus.
This relationship of binding causes the protein to go from disorder to order. Thus, pharmacological reactivation of p53 presents itself as a viable cancer treatment option.
It is beneficial to understand the mechanism of actions by which p53 regulates and stimulates cancer cell proliferation and survival of cells. Tumor suppressors such as p53, whose inactivation is required for the malignant transformation of a cell, has become one of the most researched topics in the field of cancer.
What could cause such a severe response as cell death?. Called p53, the protein sounds the alarm to kill cells with DNA damage and prevent them from becoming cancerous—one reason why it has been called the “guardian of the genome.” But it is big and floppy, a molecular shapeshifter that is hard to follow with standard imaging tools.
For this reason, p53 has often been referred to as the “Guardian of the Genome” as its sole function is in protecting the integrity of the genetic code within an organism.
Given the fact that p53 is vital for proper cell function, it is obvious to expect that when it does not have proper function, things can begin to go awry within an organism. Jul 02, · Cancer.
p53, guardian of the genome. Lane DP. Comment in Nature. Oct 8;() Comment on Nature. Jul 2;() Nature. Jul 2;() PMID: [PubMed - indexed for MEDLINE] Tumor Suppressor Protein p As such, p53 has been described as "the guardian of the genome" because of its role in conserving stability by preventing genome mutation.
Hence TP53 is classified as a tumor suppressor gene. (Italics are used to denote the TP53 gene name and distinguish it from the protein it PDB: Ortholog search: PDBe RCSB.
In cases of DNA damage, there is triggering of expression of p53 gene whcich increases the production of p53 proteins. These preoteins Prevent Cell from entering S phase of cell cycle and Allows time for the DNA repair to take.
Eg: p53, RB, BRCA1, P16 etc; Mutation of p53 is very common in many types of cancers indicating the significance of a functional p53 gene. Location: The human p53 gene is located on the seventeenth chromosome (17p). Structure The image shows a tetramer of the p53 DNA-binding domain complexed with DNA.P53 guardian of genome