title: The IKK complex contributes to the induction of autophagy.
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.
authors: INSERM, U848, Villejuif, France.
authors: Alfredo
authors: A
authors: Criollo
authors: Laura
authors: L
authors: Senovilla
authors: Hélène
authors: H
authors: Authier
authors: Maria Chiara
authors: MC
authors: Maiuri
authors: Eugenia
authors: E
authors: Morselli
authors: Ilio
authors: I
authors: Vitale
authors: Oliver
authors: O
authors: Kepp
authors: Ezgi
authors: E
authors: Tasdemir
authors: Lorenzo
authors: L
authors: Galluzzi
authors: Shensi
authors: S
authors: Shen
authors: Maximilien
authors: M
authors: Tailler
authors: Nicolas
authors: N
authors: Delahaye
authors: Antoine
authors: A
authors: Tesniere
authors: Daniela
authors: D
authors: De Stefano
authors: Aména Ben
authors: AB
authors: Younes
authors: Francis
authors: F
authors: Harper
authors: Gérard
authors: G
authors: Pierron
authors: Sergio
authors: S
authors: Lavandero
authors: Laurence
authors: L
authors: Zitvogel
authors: Alain
authors: A
authors: Israel
authors: Véronique
authors: V
authors: Baud
authors: Guido
authors: G
authors: Kroemer
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D006367:HeLa Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D041681:NIH 3T3 Cells; D015398:Signal Transduction / Q000502:physiology
chemical_list: D046912:Multiprotein Complexes; D016328:NF-kappa B; D051550:I-kappa B Kinase