Caspase 5
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Caspase 5 is an enzyme that in humans is encoded by the CASP5 gene. Caspase 5 is a member of the caspase family of cysteine proteases, which play a key role in apoptosis (programmed cell death), inflammation, and immune response. Like other caspases, caspase 5 is involved in the initiation and execution phases of cell apoptosis, acting by cleaving various cellular substrates leading to cell death. It is also implicated in the processing of inflammatory cytokines, indicating a role in the immune system beyond cell death.
Function
Caspase 5 is part of the inflammatory caspase subgroup, which also includes caspase-1 and caspase-4. These caspases are involved in the maturation of pro-inflammatory cytokines such as interleukin-1β (IL-1β) and interleukin-18 (IL-18). Caspase 5 is activated within a multiprotein complex known as the inflammasome. The inflammasome detects pathogenic microorganisms and sterile stressors, activating caspase 5 to process and secrete IL-1β and IL-18, thereby contributing to the inflammatory response.
Structure
Caspase 5 is synthesized as an inactive zymogen that is processed into active forms by self-proteolysis or by cleavage by other caspases. The active enzyme consists of a p20 subunit and a p10 subunit, forming a heterotetramer of two p20/p10 dimers. The structure of caspase 5 shares similarities with other caspases, having a large and a small subunit that together form the active site of the enzyme.
Clinical Significance
Alterations in caspase 5 expression and activity have been associated with various diseases, including inflammatory and autoimmune diseases, as well as cancer. Due to its role in inflammation and apoptosis, caspase 5 is considered a potential therapeutic target. Inhibitors of caspase 5 have been explored for the treatment of diseases characterized by excessive inflammation or unwanted cell death.
Genetic
The CASP5 gene is located on chromosome 11q22.3 in humans. Variants and mutations in this gene can affect the expression and function of caspase 5, potentially leading to disease. Research into the genetic regulation of caspase 5 and its variants may provide insights into the pathogenesis of inflammatory and autoimmune conditions, as well as cancer.
See Also
References
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Contributors: Prab R. Tumpati, MD