What triggers programmed cell death in mammals? This comprehensive review delves into the critical role of caspases, a family of cysteine-dependent aspartate-directed proteases, in apoptosis – a genetically programmed form of cell death. These death proteases, synthesized as inactive zymogens, are activated by scaffold-mediated transactivation or by cleavage via upstream proteases in an intracellular cascade. The review covers various regulatory mechanisms of caspase activation and activity, including zymogen gene transcription, antiapoptotic members of the Bcl-2 family, and cellular inhibitor of apoptosis proteins (cIAPs). Activated caspases cleave intracellular polypeptides, such as major structural elements, DNA repair machinery components, and protein kinases, disrupting survival pathways and disassembling important architectural cell components. By presenting the current understanding of **caspase structure**, **caspase activation**, and function, this study contributes to understanding the **apoptotic** process and its significance in various physiological and pathological conditions. It is crucial for researchers and clinicians to develop targeted therapies that modulate apoptosis.
As a contribution to the Annual Review of Biochemistry, this paper provides a broad overview of caspases and their function in apoptosis. This is well-suited to the journal's goal of providing in-depth reviews of significant topics in biochemistry and molecular biology, offering valuable insights for researchers and graduate students in related fields. The review helps to consolidate knowledge of a central component of biochemistry.
| Category | Category Repetition |
|---|---|
| Science: Biology (General) | 599 |
| Science: Biology (General): Cytology | 392 |
| Science: Chemistry: Organic chemistry: Biochemistry | 379 |
| Science: Biology (General): Genetics | 365 |
| Medicine: Medicine (General) | 319 |