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First published online 22 March 2005
doi: 10.1242/jcs.02295

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NACA is a positive regulator of human erythroid-cell differentiation

¹ UMR599 INSERM, 27 Blvd Leï Roure, 13009 Marseille, France
² Institut Cochin, INSERM U567, CNRS UMR 8104, Université Paris V, Département d'Hématologie, Maternité Port-Royal, 123 Blvd de Port-Royal, 75014 Paris, France
³ Genetics Unit, Shriners Hospital, 1529 Cedar Avenue, Montreal, Quebec, H3G 1A6, Canada
⁴ Institut Paoli Calmettes, 232 Blvd de Sainte Marguerite, 13273 Marseille Cedex 9, France
⁵ Hopital fondation Saint-Joseph, Maternité Ste Monique, Blvd de Louvain, 13009 Marseille, France

^* Author for correspondence (e-mail: gomez{at}marseille.inserm.fr)

Accepted 31 January 2005

We have previously identified the transcript encoding NACA (the 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.

Key words: Erythropoiesis, Cell differentiation, NACA, CD34⁺ cells, Lentiviral transduction

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