PMID- 18219697
OWN - NLM
STAT- MEDLINE
DCOM- 20080421
LR  - 20201209
IS  - 1615-9861 (Electronic)
IS  - 1615-9853 (Linking)
VI  - 8
IP  - 5
DP  - 2008 Mar
TI  - The mTOR target 4E-BP1 contributes to differential protein expression during 
      normoxia and hypoxia through changes in mRNA translation efficiency.
PG  - 1019-28
LID - 10.1002/pmic.200700551 [doi]
AB  - Hypoxia causes a rapid and sustained inhibition in mRNA translation that is 
      characterized by both a transient phosphorylation of eukaryotic initiation factor 
      2-alpha (eIF2alpha) and by inhibition of the mRNA cap binding protein eIF4E via 
      activation of two distinct inhibitory proteins, the mammalian target of rapamycin 
      (mTOR) target 4E-BP1 and the eIF4E transporter 4E-T. Although the importance of 
      eIF2alpha phosphorylation during hypoxia has been clearly demonstrated, there is 
      little information on the potential relevance of eIF4E regulation. We generated 
      HeLa cells stably expressing a short hairpin interfering RNA (shRNA) against 
      4E-BP1 and found that despite efficient knockdown, no significant changes 
      occurred in the overall inhibition of mRNA translation during hypoxia. However, 
      using a proteomics approach we identified seven proteins that were exclusively 
      expressed in the 4E-BP1 knockdown cells during both normoxic and hypoxic 
      conditions. Further investigation of the transcriptional and translational 
      regulation of these genes by quantitative RT-PCR indicated that the loss of 
      4E-BP1 causes a significant increase in the rate of protein synthesis of S100 
      calcium-binding protein A4 (S100A4) and transgelin 2. These 4E-BP1 regulated 
      proteins have previously been associated with tumor cell motility, invasion and 
      metastasis and may thus contribute to an adverse tumor phenotype.
FAU - Magagnin, Michael G
AU  - Magagnin MG
AD  - Department of Radiation Oncology (Maastro Lab), GROW Research Institute, 
      Maastricht University, Maastricht, The Netherlands.
FAU - van den Beucken, Twan
AU  - van den Beucken T
FAU - Sergeant, Kjell
AU  - Sergeant K
FAU - Lambin, Philippe
AU  - Lambin P
FAU - Koritzinsky, Marianne
AU  - Koritzinsky M
FAU - Devreese, Bart
AU  - Devreese B
FAU - Wouters, Bradly G
AU  - Wouters BG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Proteomics
JT  - Proteomics
JID - 101092707
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (EIF4EBP1 protein, human)
RN  - 0 (Microfilament Proteins)
RN  - 0 (Muscle Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (RNA, Untranslated)
RN  - 0 (S100 Calcium-Binding Protein A4)
RN  - 0 (S100 Proteins)
RN  - 0 (transgelin)
RN  - 142662-27-9 (S100A4 protein, human)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/genetics/*metabolism
MH  - Cell Cycle Proteins
MH  - Cell Proliferation
MH  - *Gene Expression Regulation
MH  - HeLa Cells
MH  - Humans
MH  - *Hypoxia
MH  - Microfilament Proteins/genetics
MH  - Muscle Proteins/genetics
MH  - Neoplasms/metabolism
MH  - Phosphoproteins/genetics/*metabolism
MH  - *Protein Biosynthesis
MH  - RNA, Untranslated/genetics
MH  - S100 Calcium-Binding Protein A4
MH  - S100 Proteins/genetics
EDAT- 2008/01/26 09:00
MHDA- 2008/04/22 09:00
CRDT- 2008/01/26 09:00
PHST- 2008/01/26 09:00 [pubmed]
PHST- 2008/04/22 09:00 [medline]
PHST- 2008/01/26 09:00 [entrez]
AID - 10.1002/pmic.200700551 [doi]
PST - ppublish
SO  - Proteomics. 2008 Mar;8(5):1019-28. doi: 10.1002/pmic.200700551.