Procaspase8at

Procaspase-8 is an inactive precursor (zymogen) of caspase-8, a key enzyme in the intrinsic and extrinsic pathways of apoptosis, the programmed cell death process. It belongs to the caspase family, which are cysteine-aspartic acid proteases that play essential roles in cell death and immune responses. Caspase-8 is primarily involved in the extrinsic pathway, where it is activated by death receptors such as TNFR1 (tumor necrosis factor receptor 1) and Fas (CD95), triggering downstream signaling that leads to apoptosis.

Procaspase-8 is synthesized as a 55-kDa polypeptide that undergoes proteolytic cleavage to form the active caspase-8 heterotetramer, consisting of two p18 and two p10 subunits. This activation typically occurs through the formation of the death-inducing signaling complex (DISC) at the cytoplasmic tail of activated death receptors. The DISC recruits adaptor proteins like FADD (Fas-associated protein with death domain) and procaspase-8, facilitating its autocatalytic cleavage and subsequent activation.

Beyond its role in apoptosis, caspase-8 also participates in non-apoptotic processes, including inflammation and cell differentiation. Dysregulation of procaspase-8 activation has been implicated in various diseases, including autoimmune disorders, neurodegenerative conditions, and cancer. Mutations or alterations in caspase-8 signaling can lead to resistance to apoptosis, contributing to tumor progression or inflammatory diseases. Research into procaspase-8 and its regulatory mechanisms continues to provide insights into therapeutic strategies for targeting apoptosis in disease treatment.