positive regulation of programmed cell death

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of programmed cell death, cell death resulting from activation of endogenous cellular processes. [GOC:jl]

Positive regulation of programmed cell death is a crucial biological process that ensures the controlled elimination of cells that are no longer needed, damaged, or potentially harmful to the organism. This process is tightly regulated and involves a complex interplay of signaling pathways, molecular mediators, and cellular machinery. Here's a detailed description of the process:

**1. Activation of Death Receptors:**
- Certain extracellular signals, such as tumor necrosis factor (TNF) or Fas ligand, bind to specific death receptors (e.g., TNFR1, Fas) on the cell surface.
- This binding triggers the recruitment of adaptor proteins, such as TRADD and FADD, which in turn activate caspase-8.

**2. Mitochondrial Pathway:**
- Intracellular stress, such as DNA damage, hypoxia, or nutrient deprivation, can activate the mitochondrial pathway.
- This pathway involves the release of pro-apoptotic proteins, including cytochrome c, from the mitochondria into the cytoplasm.
- Cytochrome c binds to Apaf-1, forming the apoptosome complex, which activates caspase-9.

**3. Caspase Activation:**
- Both the death receptor and mitochondrial pathways converge on the activation of caspases, a family of cysteine proteases.
- Caspase-8 and caspase-9 are initiator caspases that activate downstream effector caspases (e.g., caspase-3, caspase-6, caspase-7).

**4. Execution of Cell Death:**
- Activated effector caspases cleave various cellular substrates, leading to the dismantling of the cell.
- These substrates include DNA repair enzymes, cytoskeletal proteins, and nuclear lamins.
- This dismantling process results in morphological changes characteristic of apoptosis, such as cell shrinkage, nuclear fragmentation, and formation of apoptotic bodies.

**5. Phagocytosis:**
- Apoptotic bodies are efficiently phagocytosed by neighboring cells or macrophages, preventing inflammation and tissue damage.

**6. Regulation and Fine-Tuning:**
- The process of positive regulation of programmed cell death is tightly regulated by a variety of mechanisms, including:
- Anti-apoptotic proteins, such as Bcl-2 and Bcl-xL, which inhibit the release of cytochrome c from mitochondria.
- Inhibitors of apoptosis proteins (IAPs), which block the activation of caspases.
- Survival factors, such as growth factors and cytokines, which promote cell survival by activating anti-apoptotic pathways.

**In summary:**
- Positive regulation of programmed cell death is an essential process for maintaining tissue homeostasis and preventing disease.
- This process involves a complex network of signaling pathways and molecular mediators that ensure the controlled elimination of unwanted cells without causing excessive inflammation or damage to surrounding tissues.
- The intricate regulation of this process is crucial for normal development, immune function, and preventing diseases such as cancer.'
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Proteins (9)

Compounds (337)