PMID- 20421347
OWN - NLM
STAT- MEDLINE
DCOM- 20100730
LR  - 20231120
IS  - 1521-0111 (Electronic)
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 78
IP  - 1
DP  - 2010 Jul
TI  - Inhibition of human T-cell proliferation by mammalian target of rapamycin (mTOR) 
      antagonists requires noncoding RNA growth-arrest-specific transcript 5 (GAS5).
PG  - 19-28
LID - 10.1124/mol.110.064055 [doi]
AB  - The central importance of the serine/threonine protein kinase mTOR (mammalian 
      Target of Rapamycin) in the control of cell growth and proliferation is well 
      established. However, our knowledge both of the upstream pathways controlling 
      mTOR activity and of the downstream events mediating these effects is still 
      seriously incomplete. We report a previously unsuspected role for the 
      nonprotein-coding RNA GAS5 in the inhibition of T-cell proliferation produced by 
      mTOR antagonists such as rapamycin. GAS5 transcripts are up-regulated during 
      growth arrest and after rapamycin treatment, and GAS5 has recently been shown to 
      be necessary and sufficient for normal T-cell growth arrest. Down-regulation of 
      GAS5 using RNA interference protects both leukemic and primary human T cells from 
      the inhibition of proliferation produced by mTOR antagonists. The GAS5 transcript 
      is a member of the 5' terminal oligopyrimidine class of RNAs, which is 
      specifically controlled at the level of translation by the mTOR pathway, and the 
      effects of GAS5 on the cell cycle provide a novel and important link to the 
      control of proliferation. These observations point to a significant advance in 
      our understanding of the mechanism of action of mTOR inhibitors, which is likely 
      to lead to improvements in immunosuppressive and cancer therapy.
FAU - Mourtada-Maarabouni, Mirna
AU  - Mourtada-Maarabouni M
AD  - Institute for Science and Technology in Medicine and School of Life Sciences, 
      Huxley Building, Keele University, Keele, ST5 5BG, UK.
FAU - Hasan, Anwar M
AU  - Hasan AM
FAU - Farzaneh, Farzin
AU  - Farzaneh F
FAU - Williams, Gwyn T
AU  - Williams GT
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
GR  - 074452/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
DEP - 20100426
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (RNA, Small Nucleolar)
RN  - 0 (RNA, Untranslated)
RN  - 0 (growth arrest specific transcript 5)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Cell Line
MH  - Down-Regulation
MH  - Flow Cytometry
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/*antagonists & inhibitors
MH  - Leukemia/metabolism/pathology
MH  - Protein Serine-Threonine Kinases/*antagonists & inhibitors
MH  - RNA, Small Nucleolar/*physiology
MH  - RNA, Untranslated/*genetics
MH  - T-Lymphocytes/*drug effects/metabolism
MH  - TOR Serine-Threonine Kinases
PMC - PMC2912054
EDAT- 2010/04/28 06:00
MHDA- 2010/07/31 06:00
PMCR- 2011/01/01
CRDT- 2010/04/28 06:00
PHST- 2010/04/28 06:00 [entrez]
PHST- 2010/04/28 06:00 [pubmed]
PHST- 2010/07/31 06:00 [medline]
PHST- 2011/01/01 00:00 [pmc-release]
AID - mol.110.064055 [pii]
AID - 3602547 [pii]
AID - 10.1124/mol.110.064055 [doi]
PST - ppublish
SO  - Mol Pharmacol. 2010 Jul;78(1):19-28. doi: 10.1124/mol.110.064055. Epub 2010 Apr 
      26.