期刊
AUTOPHAGY
卷 5, 期 6, 页码 766-783出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/auto.8788
关键词
NF kappa B; heat shock; autophagy; protein aggregation
类别
资金
- Ligue contre le Cancer, comity du Rhone
- Region Rhone-Alpes
- French Department of Research
The heat shock response is a widely described defense mechanism during which the preferential expression of heat shock proteins (Hsps) helps the cell to recover from thermal damages such as protein denaturation/aggregation. We have previously reported that NF kappa B transcription factor is activated during the recovery period after heat shock. In this study, we analyze the consequences of NF kappa B activation during heat shock recovery, by comparing the heat shock response of NF kappa B competent and incompetent (p65/RelA-depleted) cells. We demonstrate for the first time that NF kappa B plays a major and crucial role during the heat shock response by activating autophagy, which increases survival of heat-treated cells. Indeed, we observed that autophagy is not activated during heat shock recovery and cell death is strongly increased in NF kappa B incompetent cells. Moreover, if autophagy is artificially induced in these cells, the cytotoxicity of heat shock is turned back to normal. We show that despite a post-heat shock increase of Beclin 1 level in NF kappa B competent cells, neither Beclin 1/class III PI3K complex, Bcl(2)/Bcl-X-L nor mTOR kinase are NF kappa B targets whose modulation of expression could be responsible for NF kappa B activation of autophagy during heat shock recovery. In contrast, we demonstrate that aberrantly folded/aggregated proteins are prime events in the signaling pathway leading to NF kappa B mediated autophagy after heat shock. Hence, our findings demonstrate that NF kappa B-induced autophagy during heat shock recovery is an additional cell response to HS-induced protein denaturation/aggregation; this mechanism increases cell survival, probably through clearance of irreversibly damaged proteins.
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