Premium
The IKK complex contributes to the induction of autophagy
Author(s) -
Criollo Alfredo,
Senovilla Laura,
Authier Hélène,
Maiuri Maria Chiara,
Morselli Eugenia,
Vitale Ilio,
Kepp Oliver,
Tasdemir Ezgi,
Galluzzi Lorenzo,
Shen Shensi,
Tailler Maximilien,
Delahaye Nicolas,
Tesniere Antoine,
De Stefano Daniela,
Younes Aména Ben,
Harper Francis,
Pierron Gérard,
Lavandero Sergio,
Zitvogel Laurence,
Israel Alain,
Baud Véronique,
Kroemer Guido
Publication year - 2010
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2009.364
Subject(s) - autophagy , biology , iκb kinase , microbiology and biotechnology , transcription factor , ampk , gene knockdown , phosphorylation , kinase , signal transduction , nf κb , nfkb1 , conditional gene knockout , protein kinase a , biochemistry , phenotype , gene , apoptosis
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.