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The IKK complex contributes to the induction of autophagy
- Source :
- The EMBO Journal. 29:619-631
- Publication Year :
- 2009
- Publisher :
- Wiley, 2009.
-
Abstract
- 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 (IkappaB kinase) complex that is best known for its essential role in the activation of the transcription factor NF-kappaB 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-kappaB or ablation of the p65/RelA NF-kappaB subunit failed to suppress IKK-induced autophagy, indicating that IKK can promote the autophagic pathway in an NF-kappaB-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.
- Subjects :
- Mice, Transgenic
IκB kinase
Biology
BAG3
environment and public health
Article
General Biochemistry, Genetics and Molecular Biology
Mice
chemistry.chemical_compound
Autophagy
Animals
Humans
CHUK
Molecular Biology
Transcription factor
Cells, Cultured
General Immunology and Microbiology
General Neuroscience
NF-kappa B
NF-κB
NFKB1
I-kappa B Kinase
Cell biology
Mice, Inbred C57BL
enzymes and coenzymes (carbohydrates)
chemistry
Multiprotein Complexes
NIH 3T3 Cells
biological phenomena, cell phenomena, and immunity
Signal transduction
HeLa Cells
Signal Transduction
Subjects
Details
- ISSN :
- 14602075 and 02614189
- Volume :
- 29
- Database :
- OpenAIRE
- Journal :
- The EMBO Journal
- Accession number :
- edsair.doi.dedup.....2dbf4a5ff610c59b675498c7976429c7