title: NACA is a positive regulator of human erythroid-cell differentiation.
abstract: We have previously identified the transcript encoding NACA (the alpha chain of the nascent-polypeptide-associated complex) as a cytokine-modulated specific transcript in the human TF-1 erythroleukemic cell line. This protein was already known to be a transcriptional co-activator that acts by potentiating AP-1 activity in osteoblasts, and is known to be involved in the targeting of nascent polypeptides. In this study, we investigate the role of NACA in human hematopoiesis. Protein distribution analyses indicate that NACA is expressed in undifferentiated TF-1 cells and in human-cord-blood-derived CD34(+) progenitor cells. Its expression is maintained during in vitro erythroid differentiation but, in marked contrast, its expression is suppressed during their megakaryocytic or granulocytic differentiation. Ectopic expression of NACA in CD34(+) cells under culture conditions that induce erythroid-lineage differentiation leads to a marked acceleration of erythroid-cell differentiation. Moreover, ectopic expression of NACA induces erythropoietin-independent differentiation of TF-1 cells, whereas downregulation of NACA by RNA interference abolishes the induction of hemoglobin production in these cells and diminishes glycophorin-A (GPA) expression by CD34(+) progenitors cultured under erythroid differentiation conditions. Altogether, these results characterize NACA as a new factor involved in the positive regulation of human erythroid-cell differentiation.
authors.affiliation: UMR599 INSERM, 27 Blvd Leï Roure, 13009 Marseille, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Lopez
authors.forename: Laetitia
authors.initials: L
authors.lastname: Stuhl
authors.forename: Serge
authors.initials: S
authors.lastname: Fichelson
authors.forename: Anne
authors.initials: A
authors.lastname: Dubart-Kupperschmitt
authors.forename: René
authors.initials: R
authors.lastname: St Arnaud
authors.forename: Jean-Rémy
authors.initials: JR
authors.lastname: Galindo
authors.forename: Anne
authors.initials: A
authors.lastname: Murati
authors.forename: Nicole
authors.initials: N
authors.lastname: Berda
authors.forename: Patrice
authors.initials: P
authors.lastname: Dubreuil
authors.forename: Sophie
authors.initials: S
authors.lastname: Gomez
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D045744:Cell Line, Tumor; D019070:Cell Lineage / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology; D004912:Erythrocytes / Q000378:metabolism*; D015672:Erythroid Precursor Cells / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006021:Glycophorins / Q000378:metabolism; D006098:Granulocytes / Q000378:metabolism; D006410:Hematopoiesis / Q000502:physiology*; D006454:Hemoglobins / Q000096:biosynthesis; D006801:Humans; D008533:Megakaryocytes / Q000378:metabolism; D018832:Molecular Chaperones; D034622:RNA Interference / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D018952:Antigens, CD34; D006021:Glycophorins; D006454:Hemoglobins; D018832:Molecular Chaperones; D015534:Trans-Activators; C096099:nascent-polypeptide-associated complex