positive regulation of epithelial cell apoptotic process

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of epithelial cell apoptotic process. [GO_REF:0000058, GOC:TermGenie, PMID:19137015]

Positive regulation of epithelial cell apoptotic process is a complex cellular mechanism that controls the programmed death of epithelial cells. This process is essential for maintaining tissue homeostasis, removing damaged or unwanted cells, and preventing uncontrolled cell growth. It involves a precise and tightly regulated sequence of events, initiated by a variety of signals, including intrinsic (internal) and extrinsic (external) stimuli.

**Intrinsic Pathway:**

1. **Stress or Damage Signals:** Cells under stress or damaged by factors like DNA damage, hypoxia, or nutrient deprivation activate the intrinsic pathway.
2. **Mitochondrial Membrane Permeabilization:** These signals trigger the release of pro-apoptotic proteins, like cytochrome c, from the mitochondria into the cytoplasm.
3. **Apoptosome Formation:** Cytochrome c binds to Apaf-1, a cytosolic protein, forming a complex called the apoptosome.
4. **Caspase Activation:** The apoptosome activates caspase-9, an initiator caspase, which in turn activates downstream executioner caspases (caspase-3, -6, -7).

**Extrinsic Pathway:**

1. **Death Receptor Ligand Binding:** External signals, like TNF-alpha or Fas ligand, bind to death receptors (e.g., TNF receptor 1, Fas) on the cell surface.
2. **Death-Inducing Signaling Complex (DISC) Formation:** This binding triggers the recruitment of adaptor proteins and the activation of caspase-8, an initiator caspase.
3. **Caspase Cascade Activation:** Caspase-8 activates downstream executioner caspases, leading to apoptosis.

**Execution Phase:**

1. **Caspase Activation Cascade:** Executioner caspases (caspase-3, -6, -7) are activated and cleave specific target proteins, including structural proteins, DNA repair enzymes, and inhibitors of apoptosis.
2. **Cellular Fragmentation:** These cleavages result in the breakdown of the cell into apoptotic bodies, containing cellular components, which are then phagocytosed by neighboring cells or macrophages, removing the cell without triggering an inflammatory response.

**Regulation of Apoptosis:**

* **Anti-apoptotic Proteins:** Proteins like Bcl-2 and Bcl-xL inhibit the release of cytochrome c from the mitochondria, preventing apoptosome formation and caspase activation.
* **Survival Factors:** Growth factors and cytokines can activate signaling pathways that inhibit apoptotic pathways and promote cell survival.
* **Microtubule-associated proteins (MAPs):** MAPs can regulate the activity of pro-apoptotic proteins and are involved in the organization of the cytoskeleton during apoptosis.
* **Proteasomes:** These cellular machines degrade regulatory proteins involved in apoptosis, controlling the process.

**Consequences of Dysregulation:**

* **Cancer:** Defects in apoptosis regulation can lead to uncontrolled cell growth and cancer development.
* **Autoimmune Diseases:** Excessive apoptosis can contribute to tissue damage and autoimmune disorders.
* **Neurodegenerative Diseases:** Inhibition of apoptosis in specific cell types can contribute to neurodegenerative diseases like Alzheimer's and Parkinson's.

**In summary:**

Positive regulation of epithelial cell apoptotic process is a tightly controlled mechanism that ensures the removal of unwanted or damaged epithelial cells. It involves a complex interplay of signaling pathways, pro- and anti-apoptotic proteins, and cellular machinery. The precise regulation of this process is critical for maintaining tissue homeostasis and preventing disease development.'
"

Proteins (3)

Compounds (177)