CASP8

CASP8

CASP8 (Caspase-8) is a crucial enzyme in the process of apoptosis, or programmed cell death. It is a member of the caspase family of cysteine proteases, which play essential roles in the execution phase of cell apoptosis. CASP8 is encoded by the CASP8 gene in humans.

Structure

CASP8 is synthesized as an inactive proenzyme, which undergoes proteolytic processing at conserved aspartic residues to produce two subunits, p18 and p10, that dimerize to form the active enzyme. The structure of CASP8 includes a prodomain containing two death effector domains (DEDs), which are crucial for its recruitment to the death-inducing signaling complex (DISC).

Function

CASP8 is primarily involved in the extrinsic pathway of apoptosis. It is activated upon binding to the DISC, which is formed following the engagement of death receptors such as Fas receptor (CD95) and TNF-related apoptosis-inducing ligand (TRAIL) receptors. Once activated, CASP8 can cleave and activate downstream effector caspases, such as caspase-3, leading to the execution of apoptosis.

Role in Disease

Mutations or dysregulation of CASP8 have been implicated in various diseases. For instance, reduced CASP8 activity can contribute to the development of cancer by allowing cells to evade apoptosis. Conversely, excessive CASP8 activity can lead to inappropriate cell death, contributing to neurodegenerative diseases.

Cancer

In cancer, CASP8 mutations can lead to resistance to apoptosis, allowing cancer cells to survive and proliferate. Some tumors exhibit downregulation of CASP8 expression, which is associated with poor prognosis.

Neurodegenerative Diseases

In conditions such as Alzheimer's disease and Huntington's disease, inappropriate activation of CASP8 can contribute to neuronal cell death, exacerbating disease progression.

Therapeutic Implications

Targeting CASP8 and its pathways offers potential therapeutic strategies for treating diseases characterized by either excessive or insufficient apoptosis. Inhibitors of CASP8 are being explored for their potential to protect neurons in neurodegenerative diseases, while activators of CASP8 may enhance the efficacy of cancer therapies by promoting apoptosis in tumor cells.

See Also

• Apoptosis
• Caspase family
• Death receptor

External Links

• CASP8 Gene - NCBI
• CASP8 - UniProt