PMID- 29599707
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1662-5099 (Print)
IS  - 1662-5099 (Electronic)
IS  - 1662-5099 (Linking)
VI  - 11
DP  - 2018
TI  - Brain-Derived Neurotrophic Factor Elevates Activating Transcription Factor 4 
      (ATF4) in Neurons and Promotes ATF4-Dependent Induction of Sesn2.
PG  - 62
LID - 10.3389/fnmol.2018.00062 [doi]
LID - 62
AB  - Activating transcription factor 4 (ATF4) plays important physiologic roles in the 
      brain including regulation of learning and memory as well as neuronal survival 
      and death. Yet, outside of translational regulation by the eIF2alpha-dependent stress 
      response pathway, there is little information about how its levels are controlled 
      in neurons. Here, we show that brain-derived neurotrophic factor (BDNF) promotes 
      a rapid and sustained increase in neuronal ATF4 transcripts and protein levels. 
      This increase is dependent on tropomyosin receptor kinase (TrkB) signaling, but 
      independent of levels of phosphorylated eIF2alpha. The elevation in ATF4 protein 
      occurs both in nuclei and processes. Transcriptome analysis revealed that ATF4 
      mediates BDNF-promoted induction of Sesn2 which encodes Sestrin2, a protector 
      against oxidative and genotoxic stresses and a mTor complex 1 inhibitor. In 
      contrast, BDNF-elevated ATF4 did not affect expression of a number of other known 
      ATF4 targets including several with pro-apoptotic activity. The capacity of BDNF 
      to elevate neuronal ATF4 may thus represent a means to maintain this 
      transcription factor at levels that provide neuroprotection and optimal brain 
      function without risk of triggering neurodegeneration.
FAU - Liu, Jin
AU  - Liu J
AD  - Department of Pathology and Cell Biology, Columbia University College of 
      Physicians and Surgeons, New York, NY, United States.
FAU - Amar, Fatou
AU  - Amar F
AD  - Department of Pathology and Cell Biology, Columbia University College of 
      Physicians and Surgeons, New York, NY, United States.
FAU - Corona, Carlo
AU  - Corona C
AD  - Department of Pathology and Cell Biology, Columbia University College of 
      Physicians and Surgeons, New York, NY, United States.
FAU - So, Raphaella W L
AU  - So RWL
AD  - Department of Pathology and Cell Biology, Columbia University College of 
      Physicians and Surgeons, New York, NY, United States.
FAU - Andrews, Stuart J
AU  - Andrews SJ
AD  - Department of Pathology and Cell Biology, Columbia University College of 
      Physicians and Surgeons, New York, NY, United States.
FAU - Nagy, Peter L
AU  - Nagy PL
AD  - Department of Pathology and Cell Biology, Columbia University College of 
      Physicians and Surgeons, New York, NY, United States.
FAU - Shelanski, Michael L
AU  - Shelanski ML
AD  - Department of Pathology and Cell Biology, Columbia University College of 
      Physicians and Surgeons, New York, NY, United States.
FAU - Greene, Lloyd A
AU  - Greene LA
AD  - Department of Pathology and Cell Biology, Columbia University College of 
      Physicians and Surgeons, New York, NY, United States.
LA  - eng
GR  - R01 NS033689/NS/NINDS NIH HHS/United States
GR  - R01 NS072050/NS/NINDS NIH HHS/United States
PT  - Journal Article
DEP - 20180301
PL  - Switzerland
TA  - Front Mol Neurosci
JT  - Frontiers in molecular neuroscience
JID - 101477914
PMC - PMC5863619
OTO - NOTNLM
OT  - Sestrin2
OT  - activating transcription factor 4 (ATF4)
OT  - brain-derived neurotrophic factor (BDNF)
OT  - gene regulation
OT  - neuron
OT  - neurotrophin
OT  - transcription factor
EDAT- 2018/03/31 06:00
MHDA- 2018/03/31 06:01
PMCR- 2018/01/01
CRDT- 2018/03/31 06:00
PHST- 2017/11/06 00:00 [received]
PHST- 2018/02/14 00:00 [accepted]
PHST- 2018/03/31 06:00 [entrez]
PHST- 2018/03/31 06:00 [pubmed]
PHST- 2018/03/31 06:01 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - 10.3389/fnmol.2018.00062 [doi]
PST - epublish
SO  - Front Mol Neurosci. 2018 Mar 1;11:62. doi: 10.3389/fnmol.2018.00062. eCollection 
      2018.