Apoptosis, or programmed cell death, can be activated by various factors, both internal and external to the cell.
Internal and External Triggers
- Extrinsic Pathway (Death Receptor-Mediated): Signals originating outside the cell trigger this pathway. For example, the Fas cell surface receptor induces apoptosis upon oligomerization. A protein called Daxx, identified in research (https://pubmed.ncbi.nlm.nih.gov/9215629/), binds to Fas and plays a role in activating this process.
- Intrinsic Pathway (Mitochondrial-Dependent): This pathway is activated by internal cellular stress or damage. Internal signals, such as those stemming from endoplasmic reticulum (ER) stress, can activate apoptosis. For example, the BH3-only protein Bim is essential for ER stress-induced apoptosis (https://www.sciencedirect.com/science/article/pii/S0092867407005375). Another example is the activation of apoptosis signal-regulating kinase 1 (ASK1) in response to various cellular stresses (https://pubmed.ncbi.nlm.nih.gov/8974401/). Weak external signals can also trigger the intrinsic pathway (https://en.wikipedia.org/wiki/Apoptosis).
Key Players in Apoptosis Activation
Several proteins and pathways play crucial roles in activating apoptosis. These include:
- Daxx: A protein that binds to Fas and activates JNK, a kinase involved in apoptosis (https://pubmed.ncbi.nlm.nih.gov/9215629/, https://pmc.ncbi.nlm.nih.gov/articles/PMC2989411/).
- RIP3: A receptor interacting protein kinase that activates both apoptosis and NF-κB (https://www.cell.com/current-biology/abstract/S0960-9822(99)80239-5).
- p53: A tumor suppressor protein that can induce apoptosis through various mechanisms (https://www.nature.com/articles/cdd2017169).
- Bim: A BH3-only protein crucial for ER stress-induced apoptosis (https://www.sciencedirect.com/science/article/pii/S0092867407005375).
- ASK1: A MAPKKK activated by various extracellular stimuli that can lead to apoptosis (https://pubmed.ncbi.nlm.nih.gov/8974401/, https://www.science.org/doi/10.1126/science.275.5296.90).
Both intrinsic and extrinsic pathways ultimately lead to the activation of caspases, a family of proteases that execute the cell death program (https://en.wikipedia.org/wiki/Apoptosis).
