Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.61 (caspase-8)
 6,833 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report here the identification and characterization of a new member of the mouse caspase family, named caspase-14. Northern blot analysis of mRNA from various tissues with caspase-14-specific probe showed a major transcript size of approximately 2.4 kb and variant transcripts of 2.0 kb and 1.5 kb. The major transcript is detected mainly in the liver and to a lesser extent in the brain and kidney. Caspase-14 cDNA encodes a 257-amino acid-long protein that has significant homology to other members of the caspase family. Like other caspases, caspase-14 has a conserved active site, pentapeptide QACRG. However, it lacks an NH2-terminal prodomain or a caspase recruitment domain, suggesting that it could be a downstream caspase that depends on other initiator caspases for activation. Consistent with this, procaspase-14 can be processed in vitro by the death receptor-associated caspase-8 and caspase-10 but not other caspases, and in vivo after stimulation of cells with anti-Fas agonist antibody or Tumor Necrosis Factor-Related Apoptosis Inducing Ligand. Furthermore, procaspase-14 can be cleaved by granzyme B. These observations suggest that caspase-14 may play a role in death receptor and granzyme B-induced apoptosis.
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PMID:Identification and characterization of murine caspase-14, a new member of the caspase family. 982 33

Caspase-14 is the only member of the caspase family that shows a restricted tissue expression. It is mainly confined to epidermal keratinocytes and in contrast to other caspases, is not activated during apoptosis induced by ultraviolet irradiation or cytotoxic substances. As it is cleaved under conditions leading to terminal differentiation of keratinocytes we suggested that caspase-14 plays a part in the physiologic cell death of keratinocytes leading to skin barrier formation. Here we show that retinoic acid, at concentrations inhibiting terminal differentiation of keratinocytes, strongly suppressed caspase-14 mRNA and protein expression by keratinocytes in monolayer culture and in a three-dimensional in vitro model of differentiating human epidermis (skin equivalent). By contrast, the expression of the caspases 3 and 8, which are both activated during conventional apoptosis, was increased and unchanged, respectively, after retinoic acid treatment. In addition to inhibition of differentiation in skin equivalents, retinoic acid treatment led to keratinocyte apoptosis and activation of caspase-3, both of which were undetectable in differentiated control skin equivalents. As this occurred in the absence of detectable caspase-14, our data demonstrate that caspase-14 is dispensable for keratinocyte apoptosis. The fact that in contrast to caspase-3 and caspase-8, caspase-14, similarly to other keratinocyte differentiation-associated proteins, is downregulated by retinoids, strongly suggests that this caspase, but not caspase-3 and -8, plays a part in terminal keratinocyte differentiation and skin barrier formation.
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PMID:Caspase-14 expression by epidermal keratinocytes is regulated by retinoids in a differentiation-associated manner. 1244 5