negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of intrinsic apoptotic signaling pathway by p53 class mediator. [GOC:BHF, GOC:mtg_apoptosis, GOC:rl, GOC:TermGenie, PMID:15705871]

The p53 protein is a well-known tumor suppressor that plays a crucial role in regulating cellular responses to stress. When cells encounter DNA damage, hypoxia, or other stressors, p53 is activated and can trigger various cellular responses, including cell cycle arrest, DNA repair, and apoptosis.

Apoptosis, or programmed cell death, is a tightly regulated process that eliminates damaged or unwanted cells from the body. This process is essential for maintaining tissue homeostasis and preventing the development of cancer. Apoptosis can be initiated by two main pathways: the extrinsic pathway, which is triggered by external signals like death ligands, and the intrinsic pathway, which is triggered by intracellular signals like DNA damage.

The intrinsic apoptotic pathway, also known as the mitochondrial pathway, is initiated by the release of cytochrome c from the mitochondria into the cytosol. Cytochrome c then binds to the adaptor protein Apaf-1, which activates caspase-9, an initiator caspase. Caspase-9 then activates downstream executioner caspases, such as caspase-3 and caspase-7, which dismantle the cell's structure and lead to cell death.

p53 can negatively regulate the intrinsic apoptotic signaling pathway in several ways.

One way is by activating the expression of pro-survival genes, such as Bcl-2 and Bcl-xL, which are anti-apoptotic proteins. Bcl-2 and Bcl-xL inhibit the release of cytochrome c from the mitochondria, preventing the activation of the caspase cascade and apoptosis.

Another way p53 can negatively regulate the intrinsic apoptotic pathway is by inhibiting the expression of pro-apoptotic genes, such as Bax and Bak. Bax and Bak are pro-apoptotic proteins that promote the release of cytochrome c from the mitochondria. By inhibiting the expression of these genes, p53 can prevent the activation of the intrinsic apoptotic pathway.

In addition, p53 can also directly interact with and inhibit the activity of pro-apoptotic proteins, such as Apaf-1 and caspase-9.

Overall, p53 plays a critical role in maintaining cellular homeostasis and preventing the development of cancer. By negatively regulating the intrinsic apoptotic signaling pathway, p53 can prevent premature cell death and promote cellular survival. However, when p53 is mutated or inactive, this can lead to uncontrolled cell growth and cancer development.'
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Proteins (2)

Compounds (22)