Dominant-negative c-Jun promotes neuronal survival by reducing BIM expression and inhibiting mitochondrial cytochrome c release
Details
Publication Year 2001-03,Volume 29,Issue #3,Page 629-643
Journal Title
NEURON
Publication Type
Journal Article
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 sim antisense oligonucleotides or isolated from Bim(-/-) knockout mice die more slowly after NGF withdrawal.
Publisher
CELL PRESS
Keywords
PROGRAMMED CELL-DEATH; NERVE GROWTH-FACTOR; TROPHIC FACTOR DEPRIVATION; SYMPATHETIC NEURONS; BCL-2 FAMILY; FAS LIGAND; CASPASE ACTIVATION; APOPTOSIS; BAX; PROTEIN
Terms of Use/Rights Notice
Refer to copyright notice on published article.


Creation Date: 2001-03-01 12:00:00
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