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 prolifer ation. Because the translation rate is an important determinant of cell pro liferation, we have investigated translation initiation during human myeloi d cell differentiation using the HL-60 promyelocytic leukemia cell line and the U-937 monoblastic cell line. A decrease in the translation rate is obs erved when the cells are induced to differentiate along the monocytic/macro phage pathway or along the granulocytic pathway. The inhibition in protein synthesis correlates with specific regulation of two repressors of translat ion initiation, 4E-BP1 and 4E-BP2, Induction of HL-60 and U-937 cell differ entiation into monocytes/macrophages by IFN-gamma or PMA results in a depho sphorylation and consequent activation of 4E-BP1, Dephosphorylation of 4E-B P1 was also observed when U-937 cells were induced to differentiate into mo nocytes/macrophages following treatment with retinoic acid or DMSO, In cont rast, treatment of HL-60 cells with retinoic acid or DMSO, which results in a granulocytic differentiation of these cells, decreases 4E-BP1 amount wit hout affecting its phosphorylation and strongly increases 4E-BP2 amount. Ta ken together, these data provide evidence for differential regulation of th e translational machinery during human myeloid differentiation, specific to the monocytic/macrophage pathway or to the granulocytic pathway.