Caspase-2 is essential for c-Jun transcriptional activation and Bim induction in neuron death

• Published in: Biochemical journal Vol. 455; no. 1; p. 15
• Main Authors: Jean, Ying Y, Ribe, Elena M, Pero, Maria Elena, Moskalenko, Marina, Iqbal, Zarah, Marks, Lianna J, Greene, Lloyd A, Troy, Carol M
• Format: Journal Article
• Language: English
• Published: England 01.10.2013
• Subjects: Amyloid beta-Peptides - pharmacology; Animals; Apoptosis - drug effects; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; Bcl-2-Like Protein 11; Caspase 2 - genetics; Caspase 2 - metabolism; CRADD Signaling Adaptor Protein - genetics; CRADD Signaling Adaptor Protein - metabolism; Fetus; Membrane Proteins - genetics; Membrane Proteins - metabolism; Nerve Growth Factor - deficiency; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Primary Cell Culture; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-jun - genetics; Proto-Oncogene Proteins c-jun - metabolism; Rats; Rats, Sprague-Dawley; Signal Transduction - drug effects; Transcription, Genetic - drug effects; Transcriptional Activation - drug effects
• ISSN: 1470-8728
• DOI: 10.1042/BJ20130556

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, β-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-1β-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.