PMID- 23238567
OWN - NLM
STAT- MEDLINE
DCOM- 20130911
LR  - 20230815
IS  - 1476-5403 (Electronic)
IS  - 1350-9047 (Print)
IS  - 1350-9047 (Linking)
VI  - 20
IP  - 4
DP  - 2013 Apr
TI  - Sestrin2 integrates Akt and mTOR signaling to protect cells against energetic 
      stress-induced death.
PG  - 611-9
LID - 10.1038/cdd.2012.157 [doi]
AB  - 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.
FAU - Ben-Sahra, I
AU  - Ben-Sahra I
AD  - INSERM U1065, Centre Mediterraneen de Medecine Moleculaire (C3M), Team Cellular 
      and Molecular Physiopathology of Obesity and Diabetes, Nice, France.
FAU - Dirat, B
AU  - Dirat B
FAU - Laurent, K
AU  - Laurent K
FAU - Puissant, A
AU  - Puissant A
FAU - Auberger, P
AU  - Auberger P
FAU - Budanov, A
AU  - Budanov A
FAU - Tanti, J-F
AU  - Tanti JF
FAU - Bost, F
AU  - Bost F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121214
PL  - England
TA  - Cell Death Differ
JT  - Cell death and differentiation
JID - 9437445
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (SESN2 protein, human)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - 9100L32L2N (Metformin)
RN  - 9G2MP84A8W (Deoxyglucose)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Adenosine Triphosphate/metabolism
MH  - Apoptosis/*drug effects
MH  - Caspases/metabolism
MH  - Cell Line
MH  - Deoxyglucose/*toxicity
MH  - Humans
MH  - Metformin/toxicity
MH  - Nuclear Proteins/antagonists & inhibitors/genetics/*metabolism
MH  - Phosphatidylinositol 3-Kinase/metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - RNA Interference
MH  - RNA, Small Interfering/metabolism
MH  - Signal Transduction/drug effects
MH  - Stress, Physiological/drug effects
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/*metabolism
MH  - Tumor Suppressor Protein p53/metabolism
MH  - Up-Regulation
PMC - PMC3595485
EDAT- 2012/12/15 06:00
MHDA- 2013/09/12 06:00
PMCR- 2014/04/01
CRDT- 2012/12/15 06:00
PHST- 2012/12/15 06:00 [entrez]
PHST- 2012/12/15 06:00 [pubmed]
PHST- 2013/09/12 06:00 [medline]
PHST- 2014/04/01 00:00 [pmc-release]
AID - cdd2012157 [pii]
AID - 10.1038/cdd.2012.157 [doi]
PST - ppublish
SO  - Cell Death Differ. 2013 Apr;20(4):611-9. doi: 10.1038/cdd.2012.157. Epub 2012 Dec 
      14.