PMID- 12417714
OWN - NLM
STAT- MEDLINE
DCOM- 20030102
LR  - 20211203
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 22
IP  - 23
DP  - 2002 Dec
TI  - Transduction of growth or mitogenic signals into translational activation of TOP 
      mRNAs is fully reliant on the phosphatidylinositol 3-kinase-mediated pathway but 
      requires neither S6K1 nor rpS6 phosphorylation.
PG  - 8101-13
AB  - Translation of terminal oligopyrimidine tract (TOP) mRNAs, which encode multiple 
      components of the protein synthesis machinery, is known to be controlled by 
      mitogenic stimuli. We now show that the ability of cells to progress through the 
      cell cycle is not a prerequisite for this mode of regulation. TOP mRNAs can be 
      translationally activated when PC12 or embryonic stem (ES) cells are induced to 
      grow (increase their size) by nerve growth factor and retinoic acid, 
      respectively, while remaining mitotically arrested. However, both growth and 
      mitogenic signals converge via the phosphatidylinositol 3-kinase 
      (PI3-kinase)-mediated pathway and are transduced to efficiently translate TOP 
      mRNAs. Translational activation of TOP mRNAs can be abolished by LY294002, a 
      PI3-kinase inhibitor, or by overexpression of PTEN as well as by 
      dominant-negative mutants of PI3-kinase or its effectors, PDK1 and protein kinase 
      Balpha (PKBalpha). Likewise, overexpression of constitutively active PI3-kinase 
      or PKBalpha can relieve the translational repression of TOP mRNAs in quiescent 
      cells. Both mitogenic and growth signals lead to phosphorylation of ribosomal 
      protein S6 (rpS6), which precedes the translational activation of TOP mRNAs. 
      Nevertheless, neither rpS6 phosphorylation nor its kinase, S6K1, is essential for 
      the translational response of these mRNAs. Thus, TOP mRNAs can be translationally 
      activated by growth or mitogenic stimuli of ES cells, whose rpS6 is 
      constitutively unphosphorylated due to the disruption of both alleles of S6K1. 
      Similarly, complete inhibition of mammalian target of rapamycin (mTOR) and its 
      effector S6K by rapamycin in various cell lines has only a mild repressive effect 
      on the translation of TOP mRNAs. It therefore appears that translation of TOP 
      mRNAs is primarily regulated by growth and mitogenic cues through the PI3-kinase 
      pathway, with a minor role, if any, for the mTOR pathway.
FAU - Stolovich, Miri
AU  - Stolovich M
AD  - Department of Biochemistry, The Hebrew University-Hadassah Medical School, 
      Jerusalem 91120, Israel.
FAU - Tang, Hua
AU  - Tang H
FAU - Hornstein, Eran
AU  - Hornstein E
FAU - Levy, Galit
AU  - Levy G
FAU - Cohen, Ruth
AU  - Cohen R
FAU - Bae, Sun Sik
AU  - Bae SS
FAU - Birnbaum, Morris J
AU  - Birnbaum MJ
FAU - Meyuhas, Oded
AU  - Meyuhas O
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Chromones)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Morpholines)
RN  - 0 (Peptide Elongation Factor 1)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Ribosomal Protein S6)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - 5688UTC01R (Tretinoin)
RN  - 9061-61-4 (Nerve Growth Factor)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (RPS6KA1 protein, human)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 90-kDa)
RN  - EC 2.7.11.1 (Rps6ka1 protein, mouse)
RN  - EC 2.7.11.1 (Rps6ka1 protein, rat)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Cell Cycle/*physiology
MH  - Cell Division
MH  - Cell Line
MH  - Chromones/metabolism
MH  - Enzyme Inhibitors/metabolism
MH  - Female
MH  - Humans
MH  - MAP Kinase Signaling System/*physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Morpholines/metabolism
MH  - Nerve Growth Factor/metabolism
MH  - Peptide Elongation Factor 1/metabolism
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphorylation
MH  - *Protein Biosynthesis
MH  - Protein Serine-Threonine Kinases/genetics/metabolism
MH  - *Proto-Oncogene Proteins
MH  - Proto-Oncogene Proteins c-akt
MH  - RNA, Messenger/genetics/*metabolism
MH  - Rats
MH  - Ribosomal Protein S6/genetics/*metabolism
MH  - Ribosomal Protein S6 Kinases, 90-kDa/genetics/*metabolism
MH  - Sirolimus/metabolism
MH  - Tretinoin/metabolism
PMC - PMC134064
EDAT- 2002/11/06 04:00
MHDA- 2003/01/03 04:00
PMCR- 2002/12/01
CRDT- 2002/11/06 04:00
PHST- 2002/11/06 04:00 [pubmed]
PHST- 2003/01/03 04:00 [medline]
PHST- 2002/11/06 04:00 [entrez]
PHST- 2002/12/01 00:00 [pmc-release]
AID - 0844 [pii]
AID - 10.1128/MCB.22.23.8101-8113.2002 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2002 Dec;22(23):8101-13. doi: 10.1128/MCB.22.23.8101-8113.2002.