negative regulation of epithelial cell apoptotic process

Definition

Target type: biologicalprocess

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

Negative regulation of epithelial cell apoptotic process refers to the cellular mechanisms that suppress or inhibit programmed cell death (apoptosis) specifically within epithelial tissues. Epithelial cells form linings and coverings throughout the body, playing crucial roles in protection, secretion, and absorption. Apoptosis is a tightly regulated process that eliminates damaged or unwanted cells, maintaining tissue homeostasis. Dysregulation of epithelial cell apoptosis can contribute to various diseases, including cancer and inflammatory disorders.

Key mechanisms involved in negative regulation of epithelial cell apoptotic process include:

1. Activation of survival pathways:
* **Growth factor signaling:** Growth factors like epidermal growth factor (EGF) and fibroblast growth factor (FGF) activate intracellular signaling cascades that promote cell survival by inhibiting pro-apoptotic proteins and activating anti-apoptotic proteins.
* **PI3K/AKT pathway:** This pathway is activated by growth factors and other stimuli and leads to phosphorylation and activation of the AKT protein. AKT inhibits pro-apoptotic proteins like BAD and caspase-9, while promoting the expression of anti-apoptotic proteins like Bcl-2 and Bcl-xL.
* **NF-κB signaling:** NF-κB is a transcription factor that is activated in response to stress signals and promotes the expression of anti-apoptotic genes, including IAPs (inhibitors of apoptosis proteins).

2. Inhibition of apoptotic signaling:
* **Anti-apoptotic proteins:** Bcl-2 family proteins like Bcl-2, Bcl-xL, and Mcl-1 inhibit the release of cytochrome c from mitochondria, a crucial step in the apoptotic cascade.
* **IAPs (inhibitors of apoptosis proteins):** IAPs bind to and inhibit caspases, the executioner proteases responsible for dismantling the cell during apoptosis.
* **Cellular stress response pathways:** The unfolded protein response (UPR) and the endoplasmic reticulum (ER) stress response activate signaling pathways that promote cell survival and prevent apoptosis.

3. Induction of DNA repair:
* **DNA damage response (DDR):** In response to DNA damage, cells activate repair mechanisms that aim to restore DNA integrity. Successful repair can prevent apoptosis triggered by irreparable DNA damage.

4. Cell cycle regulation:
* **Cell cycle checkpoints:** These checkpoints ensure that DNA is accurately replicated before cell division. If damage is detected, the cell cycle can be arrested to allow for DNA repair. This can prevent the propagation of damaged cells and their subsequent apoptosis.

The balance between pro-apoptotic and anti-apoptotic signals determines whether an epithelial cell survives or undergoes apoptosis. Aberrant regulation of these mechanisms can lead to the accumulation of damaged or unwanted cells, potentially contributing to the development of diseases. Understanding these complex processes is crucial for developing therapeutic strategies for various epithelial diseases.'
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Proteins (1)

Compounds (30)