期刊
EMBO JOURNAL
卷 29, 期 3, 页码 619-631出版社
WILEY
DOI: 10.1038/emboj.2009.364
关键词
hypoxia; mice; NF-kappa B; rapamycin; starvation
资金
- Ligue Nationale contre le Cancer
- Agence Nationale de la Recherche
- Canceropole Ile-de-France
- Institut National du Cancer
- European Commission
- Fondation pour la Recherche Medicale (FRM)
- ECOS-CONICYT [C08S01]
- European Union
- Agence Nationale pour la Recherche
- Association pour la Recherche sur le Cancer
- Belgian InterUniversity Attraction Pole
- UniversiteParis Descartes
- EMBO
- LG by Apo-Sys
In response to stress, cells start transcriptional and transcription-independent programs that can lead to adaptation or death. Here, we show that multiple inducers of autophagy, including nutrient depletion, trigger the activation of the IKK (I kappa B kinase) complex that is best known for its essential role in the activation of the transcription factor NF-kappa B by stress. Constitutively active IKK subunits stimulated autophagy and transduced multiple signals that operate in starvation-induced autophagy, including the phosphorylation of AMPK and JNK1. Genetic inhibition of the nuclear translocation of NF-kappa B or ablation of the p65/RelA NF-kappa B subunit failed to suppress IKK-induced autophagy, indicating that IKK can promote the autophagic pathway in an NF-kappa B-independent manner. In murine and human cells, knockout and/or knockdown of IKK subunits (but not that of p65) prevented the induction of autophagy in response to multiple stimuli. Moreover, the knockout of IKK-beta suppressed the activation of autophagy by food deprivation or rapamycin injections in vivo, in mice. Altogether, these results indicate that IKK has a cardinal role in the stimulation of autophagy by physiological and pharmacological stimuli. The EMBO Journal (2010) 29, 619-631. doi: 10.1038/emboj.2009.364; Published online 3 December 2009
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据