自噬
生物
IκB激酶
细胞生物学
转录因子
安普克
基因敲除
磷酸化
激酶
信号转导
NF-κB
NFKB1型
条件基因敲除
蛋白激酶A
生物化学
表型
基因
细胞凋亡
作者
Alfredo Criollo,Laura Senovilla,Hélène Authier,Maria Chiara Maiuri,Eugenia Morselli,Ilio Vitale,Oliver Kepp,Ezgi Tasdemir,Lorenzo Galluzzi,Shensi Shen,Maximilien Tailler,Nicolas Delahaye,Antoine Tesnière,Daniela De Stefano,Antoine Younès,Francis Harper,Gérard Pierron,Sergio Lavandero,Laurence Zitvogel,Alain Israël,Véronique Baud
标识
DOI:10.1038/emboj.2009.364
摘要
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 (IκB kinase) complex that is best known for its essential role in the activation of the transcription factor NF‐κB 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‐κB or ablation of the p65/RelA NF‐κB subunit failed to suppress IKK‐induced autophagy, indicating that IKK can promote the autophagic pathway in an NF‐κB‐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‐β 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.
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