Regulation of Autophagy by NF-kappaB Transcription Factor and Reactives Oxygen Species

Mojgan Djavaheri-Mergny, Manuella Amelotti, Julie Mathieu, Françoise Besançon, Chantal Bauvy and Patrice Codogno

volume 3 | issue 4

July/August 2007
Pages: 390 - 392

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The NF-κappaB transcription factor is an important anti-apoptotic factor, which is frequently deregulated in cancer cells. We have recently demonstrated that NF-kappaB activation mediates the repression of autophagy in response to TNFα in three models of cancer cell lines. In contrast, in the absence of NF-kappaB activation, TNFα induces autophagy, which requires reactive oxygen species (ROS) production and participates in the TNFα-induced apoptotic signaling pathway. Autophagy-dependent apoptosis was also observed following direct addition of ROS to cells. Moreover, addition of rapamycin to TNFα renders these cells susceptible to the cytotoxic effect of this cytokine. These findings highlight the regulation of autophagy by oxidative stress and support the idea that repression of autophagy by NF-kappaB may constitute a novel anti-apoptotic function of this transcription factor. We also bring evidence that direct stimulation of autophagy may represent a new therapeutic strategy for overcoming the NF-κappaB-dependent chemoresistance of cancer cells.

Addendum to:
NF-κappaB Activation Represses TNF-alpha-Induced Autophagy
M. Djavaheri-Mergny, M. Amelotti, J. Mathieu, F. Besançon, C. Bauvy, S. Souquère, G. Pierron and P. Codogno
J Biol Chem 2006; 281:30373-82

Authors

Mojgan Djavaheri-Mergny

Université Paris-Sud 11

Manuella Amelotti

Laboratory of Biochemistry and Molecular Biology

Julie Mathieu

INSERM U685

Françoise Besançon

INSERM U685

Chantal Bauvy

INSERM U756

Patrice Codogno