FADD

Extrinsic_apoptosis.jpg

FADD (Fas-Associated protein with Death Domain) is a crucial adaptor molecule involved in the process of apoptosis, or programmed cell death. It plays a significant role in the extrinsic pathway of apoptosis, which is initiated by the binding of death ligands to their corresponding death receptors on the cell surface.

Structure

FADD is composed of two main domains: the death domain (DD) and the death effector domain (DED). The death domain is responsible for interactions with the death domains of other proteins, such as the Fas receptor (also known as CD95) and TNF receptor 1. The death effector domain facilitates the recruitment of downstream signaling molecules, such as procaspase-8.

Function

FADD is primarily involved in the formation of the Death-Inducing Signaling Complex (DISC). Upon the binding of a death ligand, such as Fas ligand (FasL) or TNF-related apoptosis-inducing ligand (TRAIL), to their respective death receptors, FADD is recruited to the receptor complex through its death domain. This recruitment allows FADD to interact with procaspase-8 via its death effector domain, leading to the activation of caspase-8. Activated caspase-8 then initiates a cascade of downstream caspase activations, ultimately resulting in apoptosis.

Role in Disease

Dysregulation of FADD-mediated signaling pathways can lead to various diseases. Overactivation of FADD can result in excessive cell death, contributing to conditions such as neurodegenerative diseases and ischemic injury. Conversely, insufficient FADD activity can lead to the survival of abnormal cells, contributing to the development of cancer and autoimmune diseases.

Research and Therapeutic Potential

FADD is a target of interest in the development of therapeutic interventions for diseases characterized by abnormal apoptosis. Modulating FADD activity or its interactions with other proteins in the apoptotic pathway holds potential for the treatment of cancer, autoimmune diseases, and neurodegenerative disorders.

See also

• Apoptosis
• Caspase
• Death receptor
• Fas receptor
• TNF receptor

External links

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