PMID- 19439225
OWN - NLM
STAT- MEDLINE
DCOM- 20091113
LR  - 20211203
IS  - 1873-4596 (Electronic)
IS  - 0891-5849 (Linking)
VI  - 46
IP  - 8
DP  - 2009 Apr 15
TI  - Activating transcription factor 4 and CCAAT/enhancer-binding protein-beta 
      negatively regulate the mammalian target of rapamycin via Redd1 expression in 
      response to oxidative and endoplasmic reticulum stress.
PG  - 1158-67
LID - 10.1016/j.freeradbiomed.2009.01.015 [doi]
AB  - Regulation of mRNA translation in mammalian cells involves the coordinated 
      control of mammalian target of rapamycin (mTOR) signaling. At present, limited 
      information is available on the potential relevance of mTOR regulation, although 
      translation inhibition during oxidative and endoplasmic reticulum (ER) stress is 
      clearly important. In this study, we show that activating transcription factor 4 
      (ATF4) and CCAAT/enhancer-binding protein-beta (C/EBP-beta) negatively regulate 
      mTOR via Redd1 expression in response to oxidative and ER stress. Oxidative and 
      ER stress conditions induce rapid and significant activation of ATF4 downstream 
      of eIF2alpha phosphorylation, which is responsible for Redd1 expression. In our 
      experiment, overexpression of ATF4 was associated with reduced mTOR activity via 
      Redd1 expression, whereas suppression of ATF4 levels with small interfering RNA 
      led to the recovery of decreased mTOR activity mediated by downregulation of 
      Redd1 during oxidative and ER stress. We additionally identified Redd1 as a 
      downstream effector of C/EBP-beta stimulated by ATF4 activated under the stress 
      conditions examined. RNA interference studies provided further evidence of the 
      requirement of C/EBP-beta for Redd1 expression. We conclude that the Redd1 gene 
      is transactivated by the ATF4 and C/EBP family of transcription factors, leading 
      to mTOR inhibition in response to oxidative and ER stress.
FAU - Jin, Hyeon-Ok
AU  - Jin HO
AD  - Division of Radiation Cancer Research, Korea Institute of Radiological & Medical 
      Sciences, Nowon-gu, Seoul, Republic of Korea.
FAU - Seo, Sung-Keum
AU  - Seo SK
FAU - Woo, Sang-Hyeok
AU  - Woo SH
FAU - Kim, Eun-Sung
AU  - Kim ES
FAU - Lee, Hyung-Chahn
AU  - Lee HC
FAU - Yoo, Doo-Hyun
AU  - Yoo DH
FAU - An, Sungkwan
AU  - An S
FAU - Choe, Tae-Boo
AU  - Choe TB
FAU - Lee, Su-Jae
AU  - Lee SJ
FAU - Hong, Seok-Il
AU  - Hong SI
FAU - Rhee, Chang-Hun
AU  - Rhee CH
FAU - Kim, Jong-Il
AU  - Kim JI
FAU - Park, In-Chul
AU  - Park IC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090127
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (ATF4 protein, human)
RN  - 0 (CCAAT-Enhancer-Binding Protein-beta)
RN  - 0 (DDIT4 protein, human)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Transcription Factors)
RN  - 145891-90-3 (Activating Transcription Factor 4)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Activating Transcription Factor 4/genetics/metabolism/*physiology
MH  - CCAAT-Enhancer-Binding Protein-beta/*physiology
MH  - Endoplasmic Reticulum
MH  - Feedback, Physiological
MH  - HeLa Cells
MH  - Humans
MH  - Hydrogen Peroxide/metabolism
MH  - Oxidative Stress
MH  - Protein Kinases/genetics/metabolism
MH  - RNA, Small Interfering/genetics
MH  - Signal Transduction
MH  - Sirolimus/metabolism
MH  - TOR Serine-Threonine Kinases
MH  - Transcription Factors/genetics/*metabolism
MH  - *Transcriptional Activation
EDAT- 2009/05/15 09:00
MHDA- 2009/11/17 06:00
CRDT- 2009/05/15 09:00
PHST- 2008/09/05 00:00 [received]
PHST- 2009/01/20 00:00 [revised]
PHST- 2009/01/21 00:00 [accepted]
PHST- 2009/05/15 09:00 [entrez]
PHST- 2009/05/15 09:00 [pubmed]
PHST- 2009/11/17 06:00 [medline]
AID - S0891-5849(09)00054-9 [pii]
AID - 10.1016/j.freeradbiomed.2009.01.015 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2009 Apr 15;46(8):1158-67. doi: 
      10.1016/j.freeradbiomed.2009.01.015. Epub 2009 Jan 27.