PMID- 23747720
OWN - NLM
STAT- MEDLINE
DCOM- 20130919
LR  - 20200510
IS  - 1090-2422 (Electronic)
IS  - 0014-4827 (Linking)
VI  - 319
IP  - 13
DP  - 2013 Aug 1
TI  - eIF4E-Overexpression imparts perillyl alcohol and rapamycin-mediated regulation 
      of telomerase reverse transcriptase.
PG  - 2103-2112
LID - S0014-4827(13)00247-4 [pii]
LID - 10.1016/j.yexcr.2013.05.029 [doi]
AB  - Translation is mediated partly by regulation of free eukaryotic initiation factor 
      4E (eIF4E) levels through PI3K-Akt-mTOR signaling. Cancer cells treated with the 
      plant-derived perillyl alcohol (POH) or the mechanistic target of rapamycin 
      (mTOR) inhibitor rapamycin dephosphorylate eIF4E-binding protein (4E-BP1) and 
      attenuate cap-dependent translation. We previously showed in cancer cell lines 
      with elevated eIF4E that POH and rapamycin regulate telomerase activity through 
      this pathway. Here, immortalized Chinese hamster ovary (CHO) control cells and 
      CHO cells with forced eIF4E expression (rb4E) were used to elucidate eIF4E's role 
      in telomerase regulation by POH and rapamycin. Despite 5-fold higher eIF4E 
      amounts in rb4E, telomerase activity, telomerase reverse transcriptase (TERT) 
      mRNA, and TERT protein were nearly equivalent in control and rb4E cells. In 
      control cells, telomerase activity, TERT mRNA and protein levels were unaffected 
      by either compound. In contrast, telomerase activity and TERT protein were both 
      attenuated by either agent in rb4E cells, but without corresponding TERT mRNA 
      decreases indicating a translational/post-translational process. S6K, Akt, and 
      4E-BP1 were modulated by mTOR mediators only in the presence of increased eIF4E. 
      Thus, eIF4E-overexpression in rb4E cells enables inhibitory effects of POH and 
      rapamycin on telomerase and TERT protein. Importantly, eIF4E-overexpression 
      modifies cellular protein synthetic processes and gene regulation.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Sundin, Tabetha
AU  - Sundin T
AD  - Department of Biomedical Sciences, University of South Carolina School of 
      Medicine-Greenville, Greenville, SC 29605. Electronic address: 
      trsundin@sentara.com.
FAU - Peffley, Dennis
AU  - Peffley D
AD  - Department of Biomedical Sciences, University of South Carolina School of 
      Medicine-Greenville, Greenville, SC 29605. Electronic address: 
      PEFFLEY@greenvillemed.sc.edu.
FAU - Hentosh, Patricia
AU  - Hentosh P
AD  - Department of Biomedical Sciences, University of South Carolina School of 
      Medicine-Greenville, Greenville, SC 29605. Electronic address: phentosh@odu.edu.
LA  - eng
PT  - Journal Article
DEP - 20130606
PL  - United States
TA  - Exp Cell Res
JT  - Experimental cell research
JID - 0373226
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Eukaryotic Initiation Factor-4E)
RN  - 0 (Monoterpenes)
RN  - 319R5C7293 (perillyl alcohol)
RN  - EC 2.7.11.1 (Oncogene Protein v-akt)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - EC 2.7.7.49 (Telomerase)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology
MH  - CHO Cells
MH  - Cricetinae
MH  - Cricetulus
MH  - Enzyme Activation/drug effects
MH  - Eukaryotic Initiation Factor-4E/*genetics/metabolism/physiology
MH  - Gene Expression Regulation, Enzymologic/drug effects
MH  - Monoterpenes/*pharmacology
MH  - Oncogene Protein v-akt/metabolism
MH  - Phosphorylation/drug effects/genetics
MH  - Ribosomal Protein S6 Kinases/metabolism
MH  - Sirolimus/*pharmacology
MH  - Telomerase/*antagonists & inhibitors/genetics/metabolism
MH  - Transfection
MH  - Up-Regulation/genetics/physiology
OTO - NOTNLM
OT  - 3-[(3-Cholamidopropyl)dimethylammonio]-l-propanesulfonic acid
OT  - 3-hydroxy-3-methylglutaryl-CoA reductase
OT  - 4E T
OT  - 4E-BP1
OT  - 4E-binding protein 1
OT  - CHAPS
OT  - CHO
OT  - Chinese hamster ovary
OT  - EtOH
OT  - HMG-CoA reductase
OT  - Oncogene addiction
OT  - Oncogenic shock
OT  - P-bodies
OT  - PI3K
OT  - PI3K-Akt-mTOR pathway
OT  - POH
OT  - PVDF
OT  - RTQ-TRAP
OT  - Rapa
OT  - S6K
OT  - TERT
OT  - Telomerase activity
OT  - Telomerase reverse transcriptase
OT  - UTR
OT  - eIF4
OT  - eIF4E-overexpression
OT  - eIF4E-transporter
OT  - ethanol
OT  - eukaryotic initiation factor 4
OT  - mTOR
OT  - mechanistic target of rapamycin
OT  - p70 S6 kinase
OT  - perillyl alcohol
OT  - phosphoinositide 3-kinase
OT  - polyvinylidene fluoride
OT  - processing-bodies
OT  - rapamycin
OT  - real-time quantitative telomerase repeat amplification protocol
OT  - telomerase reverse transcriptase
OT  - untranslated region
EDAT- 2013/06/12 06:00
MHDA- 2013/09/21 06:00
CRDT- 2013/06/11 06:00
PHST- 2013/03/07 00:00 [received]
PHST- 2013/05/24 00:00 [revised]
PHST- 2013/05/27 00:00 [accepted]
PHST- 2013/06/11 06:00 [entrez]
PHST- 2013/06/12 06:00 [pubmed]
PHST- 2013/09/21 06:00 [medline]
AID - S0014-4827(13)00247-4 [pii]
AID - 10.1016/j.yexcr.2013.05.029 [doi]
PST - ppublish
SO  - Exp Cell Res. 2013 Aug 1;319(13):2103-2112. doi: 10.1016/j.yexcr.2013.05.029. 
      Epub 2013 Jun 6.