TNF-α Signaling || 4K Animation

Summary

This video explains TNF-α signaling, a key biological process that regulates cell fate by triggering two pathways: apoptosis (cell death) and survival. TNF-α binds to the TNF receptor, initiating a signaling cascade. In the apoptosis pathway, proteins like TRADD, FADD, and caspases lead to cell death, while in the survival pathway, proteins like TRAF2, RIP, IKK, and NFκB promote cell survival. The balance between these pathways is vital for preventing diseases such as cancer and autoimmune disorders. The video provides an accessible breakdown of these processes, emphasizing their significance in maintaining tissue homeostasis.

Takeaways

• 😀 TNF-α signaling regulates cell fate by activating the TNF receptor, triggering two pathways: cell death or survival.
• 😀 TNF-α is a cytokine involved in inflammation and immune responses.
• 😀 The TNF receptor, a transmembrane protein, binds with TNF-α, initiating a conformational change that exposes a death domain (DD).
• 😀 The death domain recruits TRADD, which plays a crucial role in deciding whether the cell undergoes apoptosis or survival.
• 😀 In the apoptosis pathway, TRADD interacts with FADD, which recruits procaspase 8, initiating the extrinsic apoptosis pathway.
• 😀 Procaspase 8 forms the death-inducing signaling complex (DISC), which activates caspase 8 and triggers caspase 3 to execute cell death.
• 😀 The extrinsic apoptosis pathway is triggered by an external signal like TNF-α and leads to the execution of cell death.
• 😀 In the cell survival pathway, TRADD interacts with TRAF2 and RIP to activate kinases that promote cell survival.
• 😀 The NIK-IKK complex is activated, which leads to the degradation of IκBα, releasing NFκB, a transcription factor for cell survival genes.
• 😀 NFκB activation promotes the expression of survival proteins like Bcl-2, c-IAP, and FLIP, inhibiting the apoptosis pathway.
• 😀 Balancing cell death and survival is critical for tissue homeostasis and preventing diseases like cancer and autoimmune disorders.

Q & A

What is TNF-α and what role does it play in the body?

TNF-α (Tumor Necrosis Factor alpha) is a cytokine, a type of protein that plays a key role in mediating inflammation and immune responses in the body.

How does TNF-α activate the TNF receptor?

When TNF-α binds to the TNF receptor, a transmembrane protein, it causes a conformational change in the receptor, exposing a death domain (DD) on its intracellular tail.

What happens after the death domain (DD) is exposed on the TNF receptor?

The exposed death domain recruits a protein called TRADD, which contains both a death domain (DD) and an N-terminal domain, helping determine the cell’s fate.

What are the two distinct pathways initiated by TNF-α binding to the TNF receptor?

TNF-α binding to the TNF receptor initiates two distinct pathways: one that leads to cell death (apoptosis) and another that promotes cell survival.

How does TRADD influence the fate of the cell?

TRADD acts as a molecular switch. Depending on the cellular context, it can either form a complex with FADD to trigger apoptosis or with TRAF2 and RIP to promote cell survival.

What is the role of FADD in the apoptosis pathway?

FADD, a protein containing a death domain (DD) and a death effector domain (DED), recruits procaspase 8, which forms the death-inducing signaling complex (DISC) that activates caspase 8, leading to apoptosis.

What is the role of caspase 8 in apoptosis?

Caspase 8, activated through the DISC complex, cleaves and activates caspase 3, a protease that executes cell death by cleaving various cellular proteins.

How does the survival pathway prevent apoptosis?

In the survival pathway, TRADD forms a complex with TRAF2 and RIP, activating a cascade of kinases that ultimately lead to the activation of NFκB, which promotes the expression of genes that inhibit apoptosis.

What is the role of NFκB in the cell survival pathway?

NFκB is a transcription factor that, when activated, translocates to the nucleus and promotes the transcription of genes that support cell survival, such as Bcl-2, c-IAP, and FLIP, which inhibit caspases involved in apoptosis.

Why is the balance between cell death and survival pathways important?

The balance between cell death and survival pathways is crucial for maintaining tissue homeostasis. Disruption of this balance can contribute to diseases like cancer and autoimmune disorders.