Dominant-Negative c-Jun Promotes Neuronal Survival by Reducing BIM Expression and Inhibiting Mitochondrial Cytochrome c Release

Eisai London Research Laboratories, Bernard Katz Building, University College London, Gower Street, WC1E 6BT, London, United Kingdom.
Neuron (Impact Factor: 15.98). 04/2001; 29(3):629-43. DOI: 10.1016/S0896-6273(01)00239-2
Source: PubMed

ABSTRACT Sympathetic neurons require nerve growth factor for survival and die by apoptosis in its absence. Key steps in the death pathway include c-Jun activation, mitochondrial cytochrome c release, and caspase activation. Here, we show that neurons rescued from NGF withdrawal-induced apoptosis by expression of dominant-negative c-Jun do not release cytochrome c from their mitochondria. Furthermore, we find that the mRNA for BIM(EL), a proapoptotic BCL-2 family member, increases in level after NGF withdrawal and that this is reduced by dominant-negative c-Jun. Finally, overexpression of BIM(EL) in neurons induces cytochrome c redistribution and apoptosis in the presence of NGF, and neurons injected with Bim antisense oligonucleotides or isolated from Bim(-/-) knockout mice die more slowly after NGF withdrawal.


Available from: Jonathan Whitfield, Aug 27, 2014
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