What is the role of p53 in regulating cancer?
If the DNA can be repaired, p53 activates other genes to fix the damage. If the DNA cannot be repaired, this protein prevents the cell from dividing and signals it to undergo apoptosis. By stopping cells with mutated or damaged DNA from dividing, p53 helps prevent the development of tumors.
What happens when p53 is phosphorylated?
Following stress, p53 is phosphorylated at multiple residues, thereby modifying its biochemical functions required for increased activity as a transcription factor. The biochemical functions include sequence-specific DNA binding and protein-protein interactions.
How does p53 regulate damage?
Activation of p53 in response to DNA damage is associated with a rapid increase in its levels and with an increased ability of p53 to bind DNA and mediate transcriptional activation. This then leads to the activation of a number of genes whose products trigger cell-cycle arrest, apoptosis, or DNA repair.
What is regulated by p53?
The tumour suppressor p53 has a central role in the response to cellular stress. Activated p53 transcriptionally regulates hundreds of genes that are involved in multiple biological processes, including in DNA damage repair, cell cycle arrest, apoptosis and senescence.
What kind of cancer gene is TP53?
An inherited TP53 mutation is known as Li-Fraumeni syndrome. Li-Fraumeni syndrome is a rare genetic condition that can increase your risk of certain types of cancers. These cancers include breast cancer, bone cancer, leukemia, and soft tissue cancers, also called sarcomas.
How does p53 induce apoptosis?
P53 induces apoptosis in nontransformed cells mostly by direct transcriptional activation of the pro-apoptotic BH3-only proteins PUMA and (to a lesser extent) NOXA. Combined loss of the p53 effectors of apoptosis (PUMA plus NOXA) and cell cycle arrest/cell senescence (p21) does not cause spontaneous tumour development.
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.
How does p53 regulate cell proliferation?
Early works on p53 have elucidated its canonical function in response to DNA damage. Specifically, in the presence of mild stress or damage signal, p53 blocks cell cycle progression and activates DNA repair machinery to promote cell survival and maintain genome integrity.
How does p53 regulates the cell cycle in the presence of damaged DNA?
When DNA damage is present before the entry into S phase, p53 halts the cell cycle at the G1 phase in part by transcriptionally inducing the cyclin-dependent kinase inhibitor cdkn1a, also known as p21 (el-Deiry et al. 1993).
What are two cell processes that are regulated by p53?
The p53 tumor suppressor protein is involved in diverse cellular processes, including the regulation of the cell cycle, apoptosis, senescence, DNA repair, cell differentiation and angiogenesis.
How p53 regulates the cell cycle?
It controls several genes that play a role in the arrest of the cell cycle, cellular senescence, DNA repair system, and apoptosis. P53 plays a crucial role in supporting DNA repair by arresting the cell cycle to purchase time for the repair system to restore genome stability.