Differential regulation of 4E-BP1 and 4E-BP2, two repressors of translation initiation, during human myeloid cell differentiation.
Human myeloid differentiation is accompanied by a decrease in cell proliferation. Because the translation rate is an important determinant of cell proliferation, we have investigated translation initiation during human myeloid cell differentiation using the HL-60 promyelocytic leukemia cell line and the U-937 monoblastic cell line. A decrease in the translation rate is observed when the cells are induced to differentiate along the monocytic/macrophage pathway or along the granulocytic pathway. The inhibition in protein synthesis correlates with specific regulation of two repressors of translation initiation, 4E-BP1 and 4E-BP2. Induction of HL-60 and U-937 cell differentiation into monocytes/macrophages by IFN-gamma or PMA results in a dephosphorylation and consequent activation of 4E-BP1. Dephosphorylation of 4E-BP1 was also observed when U-937 cells were induced to differentiate into monocytes/macrophages following treatment with retinoic acid or DMSO. In contrast, treatment of HL-60 cells with retinoic acid or DMSO, which results in a granulocytic differentiation of these cells, decreases 4E-BP1 amount without affecting its phosphorylation and strongly increases 4E-BP2 amount. Taken together, these data provide evidence for differential regulation of the translational machinery during human myeloid differentiation, specific to the monocytic/macrophage pathway or to the granulocytic pathway.
Grolleau
A
A
Institut National de la Santé et de la Recherche Médicale, U.365, Institut Curie, Paris, France.
Sonenberg
N
N
Wietzerbin
J
J
Beretta
L
L
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D039642:Eukaryotic Initiation Factors; D006098:Granulocytes / Q000166:cytology / Q000378:metabolism; D018922:HL-60 Cells / Q000166:cytology / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D010442:Peptide Chain Initiation, Translational; D010750:Phosphoproteins / Q000096:biosynthesis / Q000378:metabolism*; D014176:Protein Biosynthesis; D012097:Repressor Proteins / Q000096:biosynthesis / Q000378:metabolism*; D020298:U937 Cells / Q000166:cytology / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; C104151:EIF4EBP2 protein, human; D039642:Eukaryotic Initiation Factors; D010750:Phosphoproteins; D012097:Repressor Proteins