Journal
CELL DEATH AND DIFFERENTIATION
Volume 20, Issue 4, Pages 611-619Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cdd.2012.157
Keywords
cell metabolism; AMPK; apoptosis; 2-deoxyglucose; metformin; sestrin
Categories
Funding
- European Foundation for the Study of Diabetes (EFSD)
- INCA [2010-219, 2010-214]
- 'La Ligue Nationale contre le cancer'
Ask authors/readers for more resources
The phosphoinositide-3 kinase/Akt (PI3K/Akt) pathway has a central role in cancer cell metabolism and proliferation. More importantly, it is one of the cardinal pro-survival pathways mediating resistance to apoptosis. The role of Akt in response to an energetic stress is presently unclear. Here, we show that Sestrin2 (Sesn2), also known as Hi95, a p53 target gene that protects cells against oxidative and genotoxic stresses, participates in the protective role of Akt in response to an energetic stress induced by 2-deoxyglucose (2-DG). Sesn2 is upregulated in response to an energetic stress such as 2-DG and metformin, and mediates the inhibition of mammalian target of rapamycin (mTOR), the major cellular regulator of energy metabolism. The increase of Sesn2 is independent of p53 but requires the anti-apoptotic pathway, PI3K/Akt. Inhibition of Akt, as well as loss of Sesn2, sensitizes cells to 2-DG-induced apoptosis. In addition, the rescue of Sesn2 partially reverses the pro-apoptotic effects of 2-DG. In conclusion, we identify Sesn2 as a new energetic stress sensor, which appears to be protective against energetic stress-induced apoptosis that integrates the pro-survival function of Akt and the negative regulation of mTOR. Cell Death and Differentiation (2013) 20, 611-619; doi:10.1038/cdd.2012.157; published online 14 December 2012
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available