Autophagy is required for the activation of NFκB

Criollo, Alfredo; Chéreau, Fanny; Malik, Shoaib Ahmad; Niso-Santano, Mireia; Mariño, Guillermo; Galluzzi, Lorenzo; Maiuri, Maria Chiara; Baud, Véronique; Kroemer, Guido

doi:10.4161/cc.11.1.18669

Cited by 104 publications

(86 citation statements)

References 21 publications

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“…We have discussed various ways in which individual ATG proteins can modulate and amplify the activities across the entire stress network. For example, Beclin 1 plays essential roles in many membrane-trafficking pathways (17,18), competitively binds to various proteins involved in NFkB activation (104,105), and serves as a balance point between apoptosis and autophagy (12). Similarly, ATG5 increases p53 abundance and activation (69,70), not only initiating a transcriptional stress response together with autophagy but also interacting with survivin to cause chromosome passenger complex dysfunction.…”

Section: Resultsmentioning

confidence: 99%

“…Stimuli that induce autophagy, such as starvation, or drugs, such as the mTORC1 inhibitor rapamycin or the p53 inhibitor pifithrin-a, also strongly stimulate activation of IKK, translocation of NFkB/p65Rel into the nucleus, and transcriptional activation of NFkB target genes. In wild-type MEFs, the activation of the canonical NFkB pathway must be accompanied by initiation of functional autophagy (105); thus, in Atg5-or Atg7-deficient MEFs, the NFkB pathway remains largely inactive (Fig. 7).…”

Section: Nrf2mentioning

confidence: 99%

“…Reciprocally, autophagy must be functional for NFkB activation to occur (105). Stimuli that induce autophagy, such as starvation, or drugs, such as the mTORC1 inhibitor rapamycin or the p53 inhibitor pifithrin-a, also strongly stimulate activation of IKK, translocation of NFkB/p65Rel into the nucleus, and transcriptional activation of NFkB target genes.…”

Section: Nrf2mentioning

confidence: 99%

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Retrograde signaling from autophagy modulates stress responses

et al. 2017

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Macroautophagy is a process in which cytoplasmic components, including whole organelles, are degraded within lysosomes. Basally, this process is essential for homeostasis and is constitutively functional in most cells, but it can also be implemented as part of stress responses. We discuss findings showing that autophagy proteins can modulate and amplify the activities of transcription factors involved in stress responses, such as those in the p53, FOXO, MiT/TFE, Nrf2, and NFkB/Rel families. Thus, transcription factors not only amplify stress responses and autophagy but are also subject to retrograde regulation by autophagy-related proteins. Physical interactions with autophagy-related proteins, competition for activating intermediates, and "signalphagy," which is the role autophagy plays in the degradation of specific signaling proteins, together provide powerful tools for implementing negative feedback or positive feed-forward loops on the transcription factors that regulate autophagy. We present examples illustrating how this network interacts to regulate metabolic and physiologic responses.

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Section: Resultsmentioning

confidence: 99%

Section: Nrf2mentioning

confidence: 99%

Section: Nrf2mentioning

confidence: 99%

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Retrograde signaling from autophagy modulates stress responses

et al. 2017

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“…Many factors known to induce autophagy, including TNF (53), also act as NF-κB activators. Depletion of essential autophagy modulators, including Atg5, Atg7, BECN1, and Vsp34 by RNAi inhibited TNFdriven NF-κB activation in human cancer cell lines (54). Similarly, KO of the genes encoding IKKα, IKKβ, IKKγ, or their upstream activator, TAK1, reduced autophagy induced by nutrient depletion or by treatment with rapamycin or other autophagy stimulators (55).…”

Section: Relb Is Required For Rankl-induced Traf3 Lysosomal Degradatimentioning

confidence: 99%

Chloroquine reduces osteoclastogenesis in murine osteoporosis by preventing TRAF3 degradation

Xiu¹,

Xu²,

Zhao³

et al. 2013

J. Clin. Invest.

138

180

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The cytokines RANKL and TNF activate NF-κB signaling in osteoclast precursors (OCPs) to induce osteoclast (OC) formation. Conversely, TNF can limit OC formation through NF-κB p100, which acts as an inhibitor, and TNF receptor-associated receptor 3 (TRAF3); however, a role for TRAF3 in RANKL-mediated OC formation is unknown. We found that TRAF3 limits RANKL-induced osteoclastogenesis by suppressing canonical and noncanonical NF-κB signaling. Conditional OC-specific Traf3-KO (cKO) mice had mild osteoporosis and increased OC formation. RANKL induced TRAF3 degradation via the lysosome/autophagy system. The autophagy/lysosome inhibitor chloroquine reduced RANKL-induced OC formation and function by increasing TRAF3 expression in OCPs in vitro and in vivo. Although chloroquine had no effect on basal bone resorption, it inhibited parathyroid hormone-and ovariectomy-induced OC activation in WT, but not cKO, mice. Deletion of the transcription factor gene Relb resulted in increased TRAF3 expression in OCPs, which was associated with decreased RANKL-induced TRAF3 degradation. RelB directly increased expression of BECN1, a key autophagy regulator, by binding to its promoter. These data indicate that autophagic/lysosomal degradation of TRAF3 is an important step in RANKL-induced NF-κB activation in OCPs. Furthermore, treatments that increase TRAF3 levels in OCPs, including pharmacological inhibition of its degradation with compounds such as chloroquine, may limit bone destruction in common bone diseases.

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“…Previous studies have shown that RELA and NFKB1 modulate canonical autophagy and their activation mediates the repression of autophagy [53][54][55] . RELA has been reported to modulate an increase of autophagy by BECN1 [56] .…”

Section: Discussionmentioning

confidence: 97%

Identification of autophagy signaling network that contributes to stroke in the ischemic rodent brain via gene expression

et al. 2015

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Autophagy plays a vital role in cerebral ischemia and may be a potential target for developing novel therapy for stroke. In this study, we constructed an autophagy-related pathway network by analyzing the genes related to autophagy and ischemic stroke, and the risk genes were screened. Two autophagy-related modules were signifi cantly up-regulated and clustered to influence cerebral ischemia. Besides, three key modular genes (NFKB1, RELA, and STAT3) were revealed. With 5-fold cross validation, the ROC curves of NFKB1, RELA, and STAT3 were 0.8256, 0.8462, and 0.8923. They formed a complex module and competitively mediated the activation of autophagy in cerebral ischemia. In conclusion, a module containing NFKB1, RELA, and STAT3 mediates autophagy, serving as a potential biomarker for the diagnosis and therapy of ischemic stroke.

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Autophagy is required for the activation of NFκB

Cited by 104 publications

References 21 publications

Retrograde signaling from autophagy modulates stress responses

Retrograde signaling from autophagy modulates stress responses

Chloroquine reduces osteoclastogenesis in murine osteoporosis by preventing TRAF3 degradation

Identification of autophagy signaling network that contributes to stroke in the ischemic rodent brain via gene expression

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