regulation of intrinsic apoptotic signaling pathway in response to osmotic stress by p53 class mediator

Definition

Target type: biologicalprocess

Any process that modulates the frequency, rate or extent of intrinsic apoptotic signaling pathway in response to osmotic stress by p53 class mediator. [GOC:krc, GOC:mtg_apoptosis, GOC:TermGenie, PMID:16571598]

The p53 tumor suppressor protein plays a crucial role in regulating the intrinsic apoptotic signaling pathway in response to osmotic stress. This intricate process involves several key steps:

1. **Osmotic Stress Detection:** When cells encounter osmotic stress, such as hypertonicity (high solute concentration) or hypotonicty (low solute concentration), they experience disruptions in their water balance. This triggers a cascade of events involving cellular sensors, including mechanosensitive channels, that detect these changes.

2. **p53 Activation:** Osmotic stress activates the p53 pathway through multiple mechanisms. This includes:
* **Direct phosphorylation:** Stress-activated kinases, such as ATM and ATR, directly phosphorylate p53, leading to its stabilization and activation.
* **Indirect activation:** Osmotic stress can induce DNA damage, which in turn activates p53 through the DNA damage response pathway involving proteins like ATM and p53-binding protein 1 (53BP1).

3. **Transcriptional Regulation:** Activated p53 acts as a transcription factor, binding to specific DNA sequences known as p53 response elements (p53REs) located in the promoter regions of target genes. This triggers the transcription of various genes involved in apoptosis, cell cycle arrest, and DNA repair.

4. **Apoptosis Induction:**
* **Pro-apoptotic genes:** p53 upregulates the expression of pro-apoptotic genes, including Bax, Puma, and Noxa. These proteins promote mitochondrial outer membrane permeabilization (MOMP), leading to the release of cytochrome c and other apoptotic factors from the mitochondria.
* **Anti-apoptotic gene suppression:** Conversely, p53 suppresses the expression of anti-apoptotic genes such as Bcl-2 and Bcl-xL, which normally inhibit apoptosis.

5. **Caspase Activation:** The release of cytochrome c from the mitochondria activates the caspase cascade, a series of proteolytic enzymes that dismantle the cell. Caspase activation leads to the cleavage of key cellular components, including DNA, cytoskeletal proteins, and other proteins essential for cellular function.

6. **Cell Death:** The activation of caspases results in the disassembly of the cell and its eventual demise. This process is characterized by morphological changes, such as cell shrinkage, nuclear fragmentation, and the formation of apoptotic bodies.

This intricate interplay of p53 and the apoptotic pathway ensures that cells eliminate themselves when exposed to severe osmotic stress, thus preventing the propagation of damaged or dysfunctional cells. This tightly regulated process is essential for maintaining cellular homeostasis and preventing the development of diseases such as cancer.'
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Proteins (1)

Compounds (2)