PMID- 15471950
OWN - NLM
STAT- MEDLINE
DCOM- 20050303
LR  - 20211203
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 105
IP  - 4
DP  - 2005 Feb 15
TI  - Activation of the p70 S6 kinase by all-trans-retinoic acid in acute promyelocytic 
      leukemia cells.
PG  - 1669-77
AB  - Although the mechanisms by which all-trans-retinoic acid (RA) regulates gene 
      transcription are well understood, very little is known on the signaling events 
      regulating RA-dependent initiation of mRNA translation. We examined whether the 
      mammalian target of rapamycin (mTOR)/p70 S6 kinase pathway is activated by RA. RA 
      treatment of sensitive cell lines resulted in phosphorylation/activation of mTOR 
      and downstream induction of p70 S6 kinase activity. Such 
      phosphorylation/activation of p70 S6 kinase was inducible in primary acute 
      promyelocytic leukemia (APL) blasts and RA-sensitive NB-4 cells, but was 
      defective in an NB-4 variant cell line (NB-4.007/6) that is resistant to the 
      biologic effects of RA. The RA-dependent activation of p70 S6 kinase was also 
      phosphatidylinositol 3' kinase (PI3'K)-dependent, and resulted in downstream 
      phosphorylation of the S6 ribosomal protein on Ser235/236 and Ser240/244, events 
      important for initiation of translation for mRNAs with oligopyrimidine tracts in 
      their 5' untranslated region. RA treatment of leukemia cells also resulted in an 
      mTOR-mediated phosphorylation of the 4E-BP1 repressor of mRNA translation, to 
      induce its deactivation and dissociation from the eukaryotic initiation factor-4E 
      (eIF-4E) complex. Altogether, these findings provide evidence for the existence 
      of a novel RA-activated cellular pathway that regulates cap-dependent 
      translation, and strongly suggest that this cascade plays a role in the induction 
      of retinoid responses in APL cells.
FAU - Lal, Lakhvir
AU  - Lal L
AD  - Robert H. Lurie Comprehensive Cancer Center, Northwestern University Medical 
      School, Chicago, IL 60611, USA.
FAU - Li, Yongzhong
AU  - Li Y
FAU - Smith, Jessica
AU  - Smith J
FAU - Sassano, Antonella
AU  - Sassano A
FAU - Uddin, Shahab
AU  - Uddin S
FAU - Parmar, Simrit
AU  - Parmar S
FAU - Tallman, Martin S
AU  - Tallman MS
FAU - Minucci, Saverio
AU  - Minucci S
FAU - Hay, Nissim
AU  - Hay N
FAU - Platanias, Leonidas C
AU  - Platanias LC
LA  - eng
GR  - CA77816/CA/NCI NIH HHS/United States
GR  - CA94079/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20041007
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Eukaryotic Initiation Factor-4E)
RN  - 0 (Growth Inhibitors)
RN  - 0 (RNA Caps)
RN  - 452VLY9402 (Serine)
RN  - 5688UTC01R (Tretinoin)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Cell Differentiation/physiology
MH  - Cell Line, Tumor
MH  - Enzyme Activation
MH  - Eukaryotic Initiation Factor-4E/metabolism
MH  - Growth Inhibitors/pharmacology
MH  - Humans
MH  - Leukemia, Promyelocytic, Acute/*enzymology/metabolism/pathology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphorylation
MH  - Protein Kinases/metabolism/physiology
MH  - RNA Caps/metabolism
MH  - Ribosomal Protein S6 Kinases, 70-kDa/*metabolism/physiology
MH  - Serine/metabolism
MH  - Signal Transduction/physiology
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases
MH  - Tretinoin/*pharmacology
EDAT- 2004/10/09 09:00
MHDA- 2005/03/04 09:00
CRDT- 2004/10/09 09:00
PHST- 2004/10/09 09:00 [pubmed]
PHST- 2005/03/04 09:00 [medline]
PHST- 2004/10/09 09:00 [entrez]
AID - S0006-4971(20)45894-X [pii]
AID - 10.1182/blood-2004-06-2078 [doi]
PST - ppublish
SO  - Blood. 2005 Feb 15;105(4):1669-77. doi: 10.1182/blood-2004-06-2078. Epub 2004 Oct 
      7.