PMID- 24691473
OWN - NLM
STAT- MEDLINE
DCOM- 20151217
LR  - 20221207
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 4
DP  - 2014
TI  - Translational regulation of GPx-1 and GPx-4 by the mTOR pathway.
PG  - e93472
LID - 10.1371/journal.pone.0093472 [doi]
LID - e93472
AB  - Glutathione peroxidase activity was previously determined to be elevated in 
      lymphocytes obtained from patients treated with the Bcr-Abl kinase inhibitor 
      imatinib mesylate. In order to expand upon this observation, the established 
      chronic myelogenous leukemia cell lines KU812 and MEG-01 were treated with 
      imatinib and the effect on several anti-oxidant proteins was determined. The 
      levels of GPx-1 were significantly increased following treatment with imatinib. 
      This increase was not due to altered steady-state mRNA levels, and appeared to be 
      dependent on the expression of Bcr-Abl, as no increases were observed following 
      imatinib treatment of cells that did not express the fusion protein. The 
      nutrient-sensing signaling protein, mammalian target of rapamycin (mTOR), can be 
      activated by Bcr-Abl and its activity regulates the translation of many different 
      proteins. Treatment of those same cells used in the imatinib studies with 
      rapamycin, an inhibitor of mTOR, resulted in elevated GPx-1 and GPx-4 protein 
      levels independent of Bcr-Abl expression. These proteins all belong to the 
      selenoprotein family of peptides that contain the UGA-encoded amino acid 
      selenocysteine. Collectively, these data provide evidence of a novel means of 
      regulating anti-oxidants of the selenoprotein family via the mTOR pathway.
FAU - Reinke, Emily N
AU  - Reinke EN
AD  - Department of Pathology, University of Illinois at Chicago, Chicago, Illinois, 
      United States of America.
FAU - Ekoue, Dede N
AU  - Ekoue DN
AD  - Department of Pathology, University of Illinois at Chicago, Chicago, Illinois, 
      United States of America.
FAU - Bera, Soumen
AU  - Bera S
AD  - Department of Pathology, University of Illinois at Chicago, Chicago, Illinois, 
      United States of America.
FAU - Mahmud, Nadim
AU  - Mahmud N
AD  - Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, 
      United States of America.
FAU - Diamond, Alan M
AU  - Diamond AM
AD  - Department of Pathology, University of Illinois at Chicago, Chicago, Illinois, 
      United States of America.
LA  - eng
GR  - R01 CA127943/CA/NCI NIH HHS/United States
GR  - R21 CA129590/CA/NCI NIH HHS/United States
GR  - CA129590/CA/NCI NIH HHS/United States
GR  - CA127943/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140401
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Antioxidants)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Selenoproteins)
RN  - 8A1O1M485B (Imatinib Mesylate)
RN  - EC 1.11.1.12 (Phospholipid Hydroperoxide Glutathione Peroxidase)
RN  - EC 1.11.1.9 (Glutathione Peroxidase)
RN  - EC 2.7.10.2 (Fusion Proteins, bcr-abl)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
RN  - EC 1.11.1.9 (Glutathione Peroxidase GPX1)
RN  - EC 1.11.1.9 (GPX1 protein, human)
SB  - IM
MH  - Antineoplastic Agents/pharmacology
MH  - Antioxidants/metabolism
MH  - Cell Line, Tumor
MH  - Enzyme Activation/drug effects
MH  - Fusion Proteins, bcr-abl/genetics/metabolism
MH  - *Gene Expression Regulation/drug effects
MH  - Glutathione Peroxidase/*genetics/metabolism
MH  - Humans
MH  - Imatinib Mesylate/pharmacology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phospholipid Hydroperoxide Glutathione Peroxidase
MH  - *Protein Biosynthesis
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Selenoproteins/genetics/metabolism
MH  - *Signal Transduction/drug effects
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Glutathione Peroxidase GPX1
PMC - PMC3972146
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/04/03 06:00
MHDA- 2015/12/19 06:00
PMCR- 2014/04/01
CRDT- 2014/04/03 06:00
PHST- 2014/02/10 00:00 [received]
PHST- 2014/03/05 00:00 [accepted]
PHST- 2014/04/03 06:00 [entrez]
PHST- 2014/04/03 06:00 [pubmed]
PHST- 2015/12/19 06:00 [medline]
PHST- 2014/04/01 00:00 [pmc-release]
AID - PONE-D-14-06318 [pii]
AID - 10.1371/journal.pone.0093472 [doi]
PST - epublish
SO  - PLoS One. 2014 Apr 1;9(4):e93472. doi: 10.1371/journal.pone.0093472. eCollection 
      2014.