Death-inducing signaling complex

Definition

The death-inducing signaling complex (DISC) is a multiprotein complex that forms in response to the binding of death ligands to their respective death receptors on the cell surface, triggering apoptosis. This complex plays a crucial role in mediating extrinsic pathways of cell death, orchestrating a series of molecular events that lead to programmed cell death.

5 Must Know Facts For Your Next Test

1. The formation of the DISC is initiated when death ligands, such as Fas ligand or TNF-alpha, bind to their corresponding death receptors, leading to receptor clustering.
2. Upon clustering, adapter proteins such as FADD (Fas-associated death domain) are recruited to the DISC, facilitating the recruitment and activation of caspases.
3. The activation of caspase-8 within the DISC triggers a cascade of downstream caspase activations, ultimately leading to cellular dismantling and apoptosis.
4. The DISC also provides a platform for regulatory mechanisms that can modulate the sensitivity of cells to apoptotic signals, influencing cell fate decisions.
5. Dysregulation of DISC formation or function can contribute to various diseases, including cancer, where cells evade apoptosis and continue to proliferate.

Review Questions

• How does the formation of the death-inducing signaling complex (DISC) lead to apoptosis, and what key proteins are involved?
  • The formation of the DISC occurs when death ligands bind to their receptors, causing receptor clustering. This clustering recruits adapter proteins like FADD, which then facilitate the recruitment and activation of initiator caspases like caspase-8. Once activated, caspase-8 initiates a cascade of downstream caspases that ultimately execute the apoptotic program by cleaving specific cellular substrates.
• Discuss the role of adapter proteins in the assembly and function of the DISC during apoptosis.
  • Adapter proteins play a vital role in assembling the DISC by linking death receptors to initiator caspases. For example, FADD is recruited to the complex after receptor activation and serves as a bridge between the activated receptor and caspase-8. This recruitment not only stabilizes the DISC but also promotes efficient activation of caspases, thereby ensuring a swift and effective apoptotic response.
• Evaluate how alterations in DISC formation or function can contribute to disease states, particularly in cancer progression.
  • Alterations in DISC formation or function can significantly impact cellular responses to apoptotic signals. In cancer, mutations or dysregulation in components associated with the DISC may prevent proper signaling from occurring, allowing tumor cells to evade apoptosis. This evasion leads to uncontrolled cell growth and survival despite damage or abnormality, contributing to tumor progression and resistance to therapies aimed at inducing cell death.

Related terms

Apoptosis: A programmed process of cellular self-destruction that is crucial for maintaining homeostasis and eliminating damaged or unnecessary cells.

Death Receptors: Specialized receptors on the cell surface that initiate apoptotic signaling when they bind to specific ligands, such as tumor necrosis factor (TNF) or Fas ligand.

Caspases: A family of cysteine proteases that are activated during apoptosis, playing a central role in executing the death program by cleaving various cellular substrates.