Article

JNK regulates FoxO-dependent autophagy in neurons

Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Genes & development (Impact Factor: 12.64). 02/2011; 25(4):310-22. DOI: 10.1101/gad.1984311
Source: PubMed

ABSTRACT The cJun N-terminal kinase (JNK) signal transduction pathway is implicated in the regulation of neuronal function. JNK is encoded by three genes that play partially redundant roles. Here we report the creation of mice with targeted ablation of all three Jnk genes in neurons. Compound JNK-deficient neurons are dependent on autophagy for survival. This autophagic response is caused by FoxO-induced expression of Bnip3 that displaces the autophagic effector Beclin-1 from inactive Bcl-XL complexes. These data identify JNK as a potent negative regulator of FoxO-dependent autophagy in neurons.

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    • "It stimulates dendrite formation, axodendritic length, axonal regeneration, mediates fast axonal transport, and contributes to the regulation of synaptic plasticity (Bjorkblom et al., 2005; Chen et al., 2005; Zhu et al., 2005; Tararuk et al., 2006; Thomas et al., 2008a; Morfini et al., 2009; Barnat et al., 2010; Podkowa et al., 2010). At the same time it has been linked to stress-induced apoptosis in different pathological conditions as a result of its inhibition of autophagy and the induction of pro-apoptotic BCL-2 family members (Jia et al., 2006; Hubner et al., 2008; Xu et al., 2011). In our cell culture system, miR-7 and miR-153 overexpression significantly lifted SAPK/JNK activation in the MPP+-treated neurons. "
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    • "JNK can act as a negative regulator of FoxO-dependent autophagy in neurons (Xu et al., 2011). It is interesting to note that, although Atg9 overexpression activates JNK, our data showed that Atg9 overexpression could not induce autophagy in the larval fat body. "
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