Autophagy is required for the activation of NFκB

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

    Research output: Contribution to journalArticlepeer-review

    94 Citations (Scopus)

    Abstract

    It is well established that the activation of the inhibitor of NFκB (IκBα) kinase (IKK) complex is required for autophagy induction by multiple stimuli. Here, we show that - in autophagy-competent mouse embryonic fibroblasts (MEFs) - distinct autophagic triggers including starvation, mTOR inhibition with rapamycin and p53 inhibition with cyclic pifithrin α lead to the activation of IKK, followed by the phosphorylation-dependent degradation of IκBα and nuclear translocation of NFκB. Remarkably, the NFκB signaling pathway was blocked in MEFs lacking either the essential autophagy genes Atg5 or Atg7. In addition, we found that tumor necrosis factor α (TNFα)-induced NFκB nuclear translocation is abolished in both Atg5- and Atg7-deficient MEFs. Similarly, the depletion of essential autophagy modulators including ATG5, ATG7, Beclin 1 and VPS34 by RNA interference inhibited TNFα-driven NFκB activation in two human cancer cell lines. In conclusion, it appears that, at least in some instances, autophagy is required for NFκB activation, highlighting an intimate crosstalk between these two stress response signaling pathways.

    Original languageEnglish
    Pages (from-to)194-199
    Number of pages6
    JournalCell Cycle
    Volume11
    Issue number1
    DOIs
    Publication statusPublished - 1 Jan 2012

    Keywords

    • A549
    • AMPK
    • Autophagosomes
    • Dna damage foci
    • HCT 116
    • LC3

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