Executioner caspases (Caspase-3, Caspase-6, Caspase-7) (CASP3/6/7)

Executioner caspases, specifically Caspase-3, Caspase-6, and Caspase-7, are cysteine-aspartic proteases that coordinate the final stages of programmed cell death by cleaving a wide array of structural and functional cellular proteins [PMID: 10648461]. In keratinocytes, these enzymes are essential for maintaining skin homeostasis, responding to ultraviolet (UV) radiation-induced DNA damage, and facilitating the specialized terminal differentiation process known as cornification [PMID: 15647522]. Dysregulation of executioner caspase activity is implicated in various dermatological conditions; for instance, inhibited apoptosis contributes to the survival of malignant cells in squamous cell carcinoma, while excessive caspase activation is observed in inflammatory skin diseases like psoriasis and atopic dermatitis [PMID: 22453182]. Therapeutic targeting of these caspases involves the use of pan-caspase inhibitors like Emricasan to reduce tissue damage or the development of pro-apoptotic agents to treat skin cancers [Source: PubChem]. However, because these enzymes are also involved in the formation of the skin's protective barrier, pharmacological modulation must be carefully balanced to avoid disrupting epidermal integrity or promoting oncogenesis by preventing the elimination of damaged cells [PMID: 17640858].

Other names

Effector caspasesApoptosis execution caspasesCaspase-3Caspase-6Caspase-7Cysteine-aspartic acid protease 3/6/7

Executioner caspases are activated through proteolytic cleavage by initiator caspases (such as Caspase-8 or Caspase-9). Once active, they catalyze the mass proteolysis of hundreds of cellular substrates, including structural proteins and DNA repair enzymes, leading to the morphological changes characteristic of apoptosis and, in the skin, contributing to the formation of the cornified envelope.