title: S6 phosphorylation-independent pathways regulate translation of 5'-terminal oligopyrimidine tract-containing mRNAs in differentiating hematopoietic cells.
abstract: Synthesis of new ribosomes is an energy costly and thus highly regulated process. Ribosomal protein synthesis is controlled by regulating translation of the corresponding ribosomal protein (rp)mRNAs. In mammalian cells a 5'-terminal oligopyrimidine tract (TOP) is a conserved feature of these mRNAs that has been demonstrated to be essential for their translational regulation. Translation of TOP mRNAs has been proposed to be regulated by phosphorylation of ribosomal protein S6, which is a common effect of mitogenic stimulation of cells. However, as demonstrated here, S6 phosphorylation is not detectable in murine erythroleukemia (MEL) or other hematopoietic cells. The absence of S6 phosphorylation appears to be due to the action of a phosphatase that acts downstream of S6 kinase, presumably on S6 itself. Despite the absence of changes in S6 phosphorylation, translation of TOP mRNAs is repressed during differentiation of MEL cells. These data demonstrate the existence of a mechanism for regulating S6 phosphorylation that is distinct from kinase activation, as well as the existence of mechanisms for regulating translation of TOP mRNAs that are independent of S6 phosphorylation.
authors.affiliation: Department of Medicine and University/Ireland Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4937, USA.
authors.forename: Diane
authors.initials: D
authors.lastname: Barth-Baus
authors.forename: Carl A
authors.initials: CA
authors.lastname: Stratton
authors.forename: Lou
authors.initials: L
authors.lastname: Parrott
authors.forename: Howard
authors.initials: H
authors.lastname: Myerson
authors.forename: Oded
authors.initials: O
authors.lastname: Meyuhas
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Templeton
authors.forename: Gary E
authors.initials: GE
authors.lastname: Landreth
authors.forename: Jack O
authors.initials: JO
authors.lastname: Hensold
mesh_terms: D024506:5' Flanking Region; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D015536:Down-Regulation; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D014176:Protein Biosynthesis; D011743:Pyrimidines / Q000032:analysis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000737:chemistry; D038601:Ribosomal Protein S6; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D012269:Ribosomal Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D011743:Pyrimidines; D012333:RNA, Messenger; D038601:Ribosomal Protein S6; D012269:Ribosomal Proteins; D019893:Ribosomal Protein S6 Kinases