The carboxyl-terminal domain of the granulocyte colony-stimulating factor receptor uncouples ribosomal biogenesis from cell cycle progression in differentiating 32D myeloid cells.
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.
Kroll
S L
SL
Department of Medicine & University/Ireland Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
Barth-Baus
D
D
Hensold
J O
JO
D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010448:Peptide Initiation Factors / Q000378:metabolism; D010766:Phosphorylation; D014176:Protein Biosynthesis / Q000502:physiology*; D017434:Protein Structure, Tertiary; D012337:RNA, Ribosomal, 18S / Q000235:genetics / Q000378:metabolism; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000737:chemistry* / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology
D007377:Interleukin-3; D010448:Peptide Initiation Factors; D012337:RNA, Ribosomal, 18S; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor