Dual role of caspase-11 in mediating activation of caspase-1 and caspase-3 under pathological conditions.
J Cell Biol
; 149(3): 613-22, 2000 May 01.
Article
em En
| MEDLINE
| ID: mdl-10791975
ABSTRACT
Caspase-11, a member of the murine caspase family, has been shown to be an upstream activator of caspase-1 in regulating cytokine maturation. We demonstrate here that in addition to its defect in cytokine maturation, caspase-11-deficient mice have a reduced number of apoptotic cells and a defect in caspase-3 activation after middle cerebral artery occlusion (MCAO), a mouse model of stroke. Recombinant procaspase-11 can autoprocess itself in vitro. Purified active recombinant caspase-11 cleaves and activates procaspase-3 very efficiently. Using a positional scanning combinatorial library method, we found that the optimal cleavage site of caspase-11 was (I/L/V/P)EHD, similar to that of upstream caspases such as caspase-8 and -9. Our results suggest that caspase-11 is a critical initiator caspase responsible for the activation of caspase-3, as well as caspase-1 under certain pathological conditions.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Caspases
/
Caspase 1
Limite:
Animals
Idioma:
En
Revista:
J Cell Biol
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
Estados Unidos