The Carboxyl-terminal Domain of the Granulocyte Colony-stimulating Factor Receptor Uncouples Ribosomal Biogenesis from Cell Cycle Progression in Differentiating 32D Myeloid Cells

Sandra L Kroll,Diane Barth-Baus,Jack O Hensold

doi:10.1074/jbc.m109577200

Abstract

Translational regulation plays an important role in development. In terminally differentiating cells a decrease in translation rate is common, although the regulatory mechanisms are unknown. We utilized 32Dcl3 myeloblast cells to investigate translational regulation during granulocyte colony-stimulating factor (G-CSF)-induced differentiation. G-CSF causes a significant decrease in translation rate compared with interleukin-3, which is a mitogen for these cells. Although these two cytokines exhibit modest differences in their effect on translation factor phosphorylation, they exhibit dramatic differences in their effect on ribosomal abundance and ribosomal DNA transcription. However, because both cytokines stimulate cell cycling, G-CSF induces a dissociation of ribosomal biogenesis from cell cycle progression. This uncoupling of ribosomal biogenesis from cell cycle progression appears to be closely related to the transmission of a differentiation signal, because it is not observed in cells expressing a carboxyl-terminally truncated G-CSF receptor, which supports proliferation but not differentiation of these cells. Because a similar event occurs early in differentiation of murine erythroleukemic cells, this suggests that ribosomal content is a common target of differentiating agents.

Highlights

Translational regulation of gene expression plays an important role in development and is the dominant means of regulating gene expression early in development [1,2,3]
These results demonstrate that granulocyte colony-stimulating factor (G-CSF) and IL-3 have dramatically different effects on overall translation rate, these agents exhibit only modest differences in their effect on phosphorylation of eIF4E, PHAS I, or ribosomal protein S6 (rpS6)
G-CSF and IL-3 Differ in Their Effect on Translation Rate—Inducers of murine erythroleukemic (MEL) cell differentiation cause a rapid decrease in translation rate that precedes differentiation (6 – 8)

Summary

Introduction

Translational regulation of gene expression plays an important role in development and is the dominant means of regulating gene expression early in development [1,2,3]. Cells expressing a carboxyl-terminally truncated G-CSF receptor that supports 32D cell proliferation but not differentiation do not demonstrate this dissociation of ribosomal content from cell cycling in response to G-CSF. To determine whether a similar effect occurred during G-CSF induced myeloid differentiation, as well as to facilitate investigation of the signaling pathways affected, growth factor-dependent 32D cells were utilized.

Results

Conclusion