What is the main function of p53?
The p53 protein is a key cell cycle regulator that manages the response to stress signals either by inducing cell growth arrest, senescence or apoptosis. The nature and intensity of stress signal, the cell type, and the cellular context dictate the final outcome.
What is p53 and what role does it play in cancer?
By stopping cells with mutated or damaged DNA from dividing, p53 helps prevent the development of tumors. Because p53 is essential for regulating DNA repair and cell division, it has been nicknamed the “guardian of the genome.”
How does radiation affect p53?
Upon radiation exposure, activation of the DNA damage response increases the level of p53 protein in cells primarily by promoting protein translation (5) and inhibiting protein degradation (6).
How does gendicine work?
Peng: Upon intratumor injection, Gendicine binds to the coxsakie adenovirus receptor (CAR) on tumor cells. Subsequently, Gendicine enters tumor cells via receptor-mediated endocytosis and begins to over-express the encoded exogenous p53 gene. The over-expressed p53 protein triggers multiple tumor fighting functions.
How does p53 act as a transcription factor?
The p53 tumor suppressor induces the transcription of genes that negatively regulate progression of the cell cycle in response to DNA damage or other cellular stressors and thus participates in maintaining genome stability.
What happens when p53 is activated?
Upon activation, p53 induces the expression of a variety of gene products, which cause either a prolonged cell-cycle arrest in G1, thereby preventing proliferation of damaged cells, or apoptosis, thereby removing damaged cells from our body.
What happens to p53 in cancer?
Mutations (changes) in the p53 gene may cause cancer cells to grow and spread in the body. These changes have been found in a genetic condition called Li-Fraumeni syndrome and in many types of cancer. The p53 gene is a type of tumor suppressor gene.
What is p53 and why does a loss of function mutation at p53 leads to cancer or uncontrolled cell growth?
In most cases, the p53 gene is mutated, giving rise to a stable mutant protein whose accumulation is regarded as a hallmark of cancer cells. Mutant p53 proteins not only lose their tumor suppressive activities but often gain additional oncogenic functions that endow cells with growth and survival advantages.
Why are cells from at patients sensitive to ionizing radiation?
The term “radiation sensitivity” describes the sensitivity of organisms to the effect of ionising radiation. The cause of radiation sensitivity may be the insufficient repair and/or misrepair of the radiation-damaged genetic material of the cells ( DNA ), for instance due to defective repair mechanisms.
How does p53 gene therapy work?
In cases where the DNA damage is irreparable, the p53 gene initiates a process called apoptosis that destroys the cancer cell before it reproduces itself. The p53 gene can also limit blood flow to tumors, which prevents growth and alerts nearby immune cells to attack cancer cells.
How does rexin G work?
The tumor-targeted gene therapy, known as DeltaRex-G (formerly Rexin-G), works by delivering a retroviral vector to tumor cells that encodes for an anticyclin G1 construct that is meant to inhibit the cyclin G1 gene (CCNG1), leading to cell death.
Does p53 increase transcription?
How are p53 and rad9 involved in DNA damage response?
RAD9 also plays a prominent role in the DNA damage response, through a variety of mechanisms, but notably also by transactivating genes. Moreover, studies thus far indicate that at least one and likely many target genes are regulated by both p53 and RAD9 interacting with the same DNA consensus sequences.
What are the functions of the p53 protein?
•p53 can be divided into at least five functional domains involved in transcriptional activation, sequence-specific DNA binding, non-specific DNA binding, oligomerization, and binding by the MDM2 protein are indicated. •Boxes I-V indicate distinct regions of p53 that are highly conserved between p53 proteins of diverse species.
How does p53 function as a tumour suppressor?
The p53 protein is a nuclear DNA-binding phosphoprotein that binds as a tetramer to p53-dependent promoters and activates the expression of downstream genes that inhibit the growth of aberrant cells [3]. Thus, p53 functions as a tumour suppressor.
How is the half life of p53 determined?
•p53 protein has a short half life (5-20 min). The amount p53 protein in cells is determined mainly by the rate at which it is degraded, rather than the rate at which it is made. •p53 degradation proceeds through ubiquitinmediated proteolysis.