CASP3 Human

Caspase 3, also known as CASP3, is a crucial enzyme in the process of apoptosis, or programmed cell death. It belongs to the family of cysteine-aspartic acid proteases, which are essential for maintaining cellular homeostasis and executing apoptosis. Caspase 3 is often referred to as an executioner caspase due to its pivotal role in the final stages of apoptosis.

Caspase 3 is synthesized as an inactive zymogen, known as procaspase-3. Upon receiving apoptotic signals, procaspase-3 is cleaved by initiator caspases, such as caspase 8 and caspase 9, into its active form. The active enzyme consists of two large and two small subunits that form a heterotetramer. This activation process is tightly regulated to ensure that apoptosis occurs only when necessary.

Caspase 3 plays a central role in the execution phase of apoptosis. It cleaves various substrates within the cell, leading to the characteristic morphological and biochemical changes associated with apoptosis. Some of its key substrates include:

• Poly (ADP-ribose) polymerase (PARP): Cleavage of PARP by caspase 3 inactivates this DNA repair enzyme, preventing the cell from repairing DNA damage and promoting cell death.
• Sterol regulatory element-binding proteins (SREBPs): Caspase 3 cleaves and activates these proteins, which are involved in lipid metabolism.
• Other caspases: Caspase 3 activates other executioner caspases, such as caspase 6 and caspase 7, amplifying the apoptotic signal.

Caspase 3 is ubiquitously expressed in various tissues, reflecting its fundamental role in apoptosis. Its expression is particularly high in tissues with high turnover rates, such as the immune system and epithelial tissues. The regulation of caspase 3 expression is complex and involves multiple signaling pathways that respond to cellular stress, DNA damage, and developmental cues.

The activity of caspase 3 is tightly regulated at multiple levels:

• Inhibitors of Apoptosis Proteins (IAPs): These proteins bind to and inhibit active caspases, including caspase 3, preventing unintended apoptosis.
• Post-translational Modifications: Caspase 3 can be regulated by phosphorylation and other modifications that affect its stability and activity.
• Transcriptional Regulation: The expression of caspase 3 is controlled by various transcription factors that respond to apoptotic signals.

Dysregulation of caspase 3 activity is implicated in numerous diseases. Overactivation of caspase 3 can lead to excessive cell death, contributing to neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. Conversely, insufficient caspase 3 activity can result in the survival of damaged cells, promoting cancer development. As a result, caspase 3 is a target for therapeutic interventions aimed at modulating apoptosis in various diseases.