Caspase-2 is essential for c-Jun transcriptional activation and Bim induction in neuron death.
Biochem J
; 455(1): 15-25, 2013 Oct 01.
Article
em En
| MEDLINE
| ID: mdl-23815625
ABSTRACT
Neuronal apoptotic death generally requires de novo transcription, and activation of the transcription factor c-Jun has been shown to be necessary in multiple neuronal death paradigms. Caspase-2 has been implicated in death of neuronal and non-neuronal cells, but its relationship to transcriptional activation has not been clearly elucidated. In the present study, using two different neuronal apoptotic paradigms, ß-amyloid treatment and NGF (nerve growth factor) withdrawal, we examined the hierarchical role of caspase-2 activation in the transcriptional control of neuron death. Both paradigms induce rapid activation of caspase-2 as well as activation of the transcription factor c-Jun and subsequent induction of the pro-apoptotic BH3 (Bcl-homology domain 3)-only protein Bim (Bcl-2-interacting mediator of cell death). Caspase-2 activation is dependent on the adaptor protein RAIDD {RIP (receptor-interacting protein)-associated ICH-1 [ICE (interleukin-1ß-converting enzyme)/CED-3 (cell-death determining 3) homologue 1] protein with a death domain}, and both caspase-2 and RAIDD are required for c-Jun activation and Bim induction. The present study thus shows that rapid caspase-2 activation is essential for c-Jun activation and Bim induction in neurons subjected to apoptotic stimuli. This places caspase-2 at an apical position in the apoptotic cascade and demonstrates for the first time that caspase-2 can regulate transcription.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ativação Transcricional
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Proteínas Proto-Oncogênicas
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Proteínas Proto-Oncogênicas c-jun
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Proteínas Reguladoras de Apoptose
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Caspase 2
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Proteína Adaptadora de Sinalização CRADD
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Proteínas de Membrana
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Neurônios
Limite:
Animals
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article