PMID- 18625885
OWN - NLM
STAT- MEDLINE
DCOM- 20081009
LR  - 20211203
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 112
IP  - 7
DP  - 2008 Oct 1
TI  - Igbp1 is part of a positive feedback loop in stem cell factor-dependent, 
      selective mRNA translation initiation inhibiting erythroid differentiation.
PG  - 2750-60
LID - 10.1182/blood-2008-01-133140 [doi]
AB  - Stem cell factor (SCF)-induced activation of phosphoinositide-3-kinase (PI3K) is 
      required for transient amplification of the erythroblast compartment. PI3K 
      stimulates the activation of mTOR (target of rapamycin) and subsequent release of 
      the cap-binding translation initiation factor 4E (eIF4E) from the 4E-binding 
      protein 4EBP, which controls the recruitment of structured mRNAs to polysomes. 
      Enhanced expression of eIF4E renders proliferation of erythroblasts independent 
      of PI3K. To investigate which mRNAs are selectively recruited to polysomes, we 
      compared SCF-dependent gene expression between total and polysome-bound mRNA. 
      This identified 111 genes primarily subject to translational regulation. For 8 of 
      9 genes studied in more detail, the SCF-induced polysome recruitment of 
      transcripts exceeded 5-fold regulation and was PI3K-dependent and 
      eIF4E-sensitive, whereas total mRNA was not affected by signal transduction. One 
      of the targets, Immunoglobulin binding protein 1 (Igbp1), is a regulatory subunit 
      of protein phosphatase 2A (Pp2a) sustaining mTOR signaling. Constitutive 
      expression of Igbp1 impaired erythroid differentiation, maintained 4EBP and 
      p70S6k phosphorylation, and enhanced polysome recruitment of multiple 
      eIF4E-sensitive mRNAs. Thus, PI3K-dependent polysome recruitment of Igbp1 acts as 
      a positive feedback mechanism on translation initiation underscoring the 
      important regulatory role of selective mRNA recruitment to polysomes in the 
      balance between proliferation and maturation of erythroblasts.
FAU - Grech, Godfrey
AU  - Grech G
AD  - Department of Hematology, Erasmus Medical Centre, Rotterdam, The Netherlands.
FAU - Blazquez-Domingo, Montserrat
AU  - Blazquez-Domingo M
FAU - Kolbus, Andrea
AU  - Kolbus A
FAU - Bakker, Walbert J
AU  - Bakker WJ
FAU - Mullner, Ernst W
AU  - Mullner EW
FAU - Beug, Hartmut
AU  - Beug H
FAU - von Lindern, Marieke
AU  - von Lindern M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080714
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Eukaryotic Initiation Factor-4E)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Stem Cell Factor)
RN  - 0 (Transforming Growth Factor beta)
RN  - 11096-26-7 (Erythropoietin)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Cell Differentiation/*drug effects
MH  - Cell Proliferation/drug effects
MH  - Cluster Analysis
MH  - Enzyme Activation/drug effects
MH  - Erythroblasts/cytology/drug effects
MH  - Erythroid Cells/*cytology/*drug effects
MH  - Erythropoietin/pharmacology
MH  - Eukaryotic Initiation Factor-4E/metabolism
MH  - Feedback, Physiological/*drug effects
MH  - Intracellular Signaling Peptides and Proteins/*metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphorylation/drug effects
MH  - Polyribosomes/drug effects/enzymology
MH  - Protein Biosynthesis/*drug effects
MH  - Protein Kinases/metabolism
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - Stem Cell Factor/*pharmacology
MH  - TOR Serine-Threonine Kinases
MH  - Transforming Growth Factor beta/pharmacology
EDAT- 2008/07/16 09:00
MHDA- 2008/10/10 09:00
CRDT- 2008/07/16 09:00
PHST- 2008/07/16 09:00 [pubmed]
PHST- 2008/10/10 09:00 [medline]
PHST- 2008/07/16 09:00 [entrez]
AID - S0006-4971(20)59800-5 [pii]
AID - 10.1182/blood-2008-01-133140 [doi]
PST - ppublish
SO  - Blood. 2008 Oct 1;112(7):2750-60. doi: 10.1182/blood-2008-01-133140. Epub 2008 
      Jul 14.