PMID- 24018049
OWN - NLM
STAT- MEDLINE
DCOM- 20141203
LR  - 20211203
IS  - 1873-3913 (Electronic)
IS  - 0898-6568 (Print)
IS  - 0898-6568 (Linking)
VI  - 25
IP  - 12
DP  - 2013 Dec
TI  - Regulated in DNA damage and development 1 (REDD1) promotes cell survival during 
      serum deprivation by sustaining repression of signaling through the mechanistic 
      target of rapamycin in complex 1 (mTORC1).
PG  - 2709-16
LID - S0898-6568(13)00275-1 [pii]
LID - 10.1016/j.cellsig.2013.08.038 [doi]
AB  - Regulated in DNA damage and development 1 (REDD1) functions to repress signaling 
      through the mechanistic target of rapamycin (mTOR) protein kinase in complex 1 
      (mTORC1) in response to diverse stress conditions. In the present study, we 
      investigated the role of REDD1 in the response of cells to growth cessation 
      induced by serum deprivation. REDD1 expression was induced within 2h of depriving 
      cells of serum, with the induction being mediated through ER stress, as evidenced 
      by activation of PERK, enhanced eIF2alpha phosphorylation, and ATF4 facilitated 
      transcription of the REDD1 gene. In wild-type cells, signaling through mTORC1 was 
      rapidly (within 30min) repressed in response to serum deprivation and the 
      repression was sustained for at least 10h. In contrast, in REDD1 knockout cells 
      mTORC1 signaling recovered toward the end of the 10h-deprivation period. 
      Interestingly, Akt phosphorylation initially declined in response to serum 
      deprivation and then recovered between 2 and 4h in wild-type but not REDD1 
      knockout cells. The recovery of mTORC1 signaling and the failure of Akt 
      phosphorylation to do so in the REDD1 knockout cells were accompanied by a 
      dramatic increase in caspase-3 cleavage and cell death, both of which were 
      blocked by rapamycin. Furthermore, overexpression of constitutively active Akt 
      rescued REDD1 knockout cells from serum deprivation induced cell death. Overall, 
      the results implicate REDD1 as a key regulatory checkpoint that coordinates 
      growth signaling inputs to activate pro-survival mechanisms and reduce 
      susceptibility to cell death.
CI  - (c) 2013.
FAU - Dennis, Michael D
AU  - Dennis MD
AD  - Department of Cellular and Molecular Physiology, The Pennsylvania State 
      University College of Medicine, Hershey, Pennsylvania 17033, USA.
FAU - McGhee, Nora K
AU  - McGhee NK
FAU - Jefferson, Leonard S
AU  - Jefferson LS
FAU - Kimball, Scot R
AU  - Kimball SR
LA  - eng
GR  - R01 DK015658/DK/NIDDK NIH HHS/United States
GR  - R01 DK013499/DK/NIDDK NIH HHS/United States
GR  - R00 EY023612/EY/NEI NIH HHS/United States
GR  - DK13499/DK/NIDDK NIH HHS/United States
GR  - EY023612/EY/NEI NIH HHS/United States
GR  - DK15658/DK/NIDDK NIH HHS/United States
GR  - K99 EY023612/EY/NEI NIH HHS/United States
GR  - F32 DK088416/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130907
PL  - England
TA  - Cell Signal
JT  - Cellular signalling
JID - 8904683
RN  - 0 (Atf4 protein, rat)
RN  - 0 (Ddit4 protein, rat)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Repressor Proteins)
RN  - 0 (Transcription Factors)
RN  - 145891-90-3 (Activating Transcription Factor 4)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Activating Transcription Factor 4/metabolism
MH  - Animals
MH  - Autophagy
MH  - Cell Line
MH  - Cell Survival
MH  - *DNA Damage
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Multiprotein Complexes/*metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats
MH  - Repressor Proteins/genetics/*metabolism
MH  - Serum/metabolism
MH  - *Signal Transduction
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Transcription Factors
MH  - Transcriptional Activation
PMC - PMC3867791
MID - NIHMS530155
OTO - NOTNLM
OT  - 4E-BP1
OT  - 70-kDa ribosomal protein S6 kinase 1
OT  - ATF4
OT  - Autophagy
OT  - DDIT4
OT  - ERK
OT  - FBS
OT  - GCN2
OT  - IGF1
OT  - LC3
OT  - PERK
OT  - REDD1
OT  - Rtp801
OT  - ULK1
OT  - UNC-51-like kinase 1
OT  - X-box binding protein 1
OT  - XBP1
OT  - activating transcription factor 4
OT  - autophagy marker light chain 3
OT  - ca
OT  - constitutively active
OT  - dn
OT  - dominant negative
OT  - eukaryotic initiation factor 4E binding protein 1
OT  - extracellular signal-related protein kinase
OT  - fetal bovine serum
OT  - general control non-derepressing 2
OT  - insulin-like growth factor 1
OT  - mTORC1
OT  - mammalian target of rapamycin in complex 1
OT  - p70S6K1
OT  - protein kinase RNA-like endoplasmic reticulum kinase
OT  - regulated in DNA damage and development 1
EDAT- 2013/09/11 06:00
MHDA- 2014/12/15 06:00
PMCR- 2014/12/01
CRDT- 2013/09/11 06:00
PHST- 2013/08/16 00:00 [received]
PHST- 2013/08/30 00:00 [accepted]
PHST- 2013/09/11 06:00 [entrez]
PHST- 2013/09/11 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
PHST- 2014/12/01 00:00 [pmc-release]
AID - S0898-6568(13)00275-1 [pii]
AID - 10.1016/j.cellsig.2013.08.038 [doi]
PST - ppublish
SO  - Cell Signal. 2013 Dec;25(12):2709-16. doi: 10.1016/j.cellsig.2013.08.038. Epub 
      2013 Sep 7.