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Blood, Vol. 92 No. 4 (August 15), 1998: pp. 1225-1234

Bcl-3 Expression and Nuclear Translocation Are Induced by Granulocyte-Macrophage Colony-Stimulating Factor and Erythropoietin in Proliferating Human Erythroid Precursors

Min-Ying Zhang, Edward W. Harhaj, Laurie Bell, Shao-Cong Sun, and Barbara A. Miller

From the Departments of Pediatrics and Microbiology and Immunology, The Pennsylvania State University College of Medicine, The Milton S. Hershey Medical Center, Hershey, PA.

Bcl-3 is a proto-oncogene involved in the chromosomal translocation t(14;19) found in some patients with chronic lymphocytic leukemia. It shares structural similarities with and is a member of the Ikappa B family of proteins. In this report, involvement of Bcl-3 in hematopoietic growth factor-stimulated erythroid proliferation and differentiation was examined. In TF-1 cells, an erythroleukemia cell line, granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (Epo) greatly enhanced Bcl-3 expression at both the protein and mRNA levels in association with stimulation of proliferation. Bcl-3 protein was also highly expressed in early burst-forming unit-erythroid (BFU-E)-derived erythroid precursors (day 7) and decreased during maturation (days 10 and 14), suggesting that Bcl-3 is involved in normal erythroid proliferation. In these hematopoietic cells, Bcl-3 was hyperphosphorylated. GM-CSF and Epo modulated the subcellular localization of Bcl-3. Upon stimulation of TF-1 cells with GM-CSF or Epo, the nuclear translocation of Bcl-3 was dramatically enhanced. Overexpression of Bcl-3 in TF-1 cells by transient transfection along with the NF-kappa B factors p50 or p52 resulted in significant induction of an human immunodeficiency virus-type 1 (HIV-1) kappa B-TATA-luceriferase reporter plasmid, demonstrating that Bcl-3 has a positive role in transactivation of kappa B-containing genes in erythroid cells. Stimulation with GM-CSF enhanced c-myb mRNA expression in these cells. Bcl-3 in nuclear extracts of TF-1 cells bound to a kappa B enhancer in the c-myb promoter together with NF-kappa B2/p52 and this binding activity was enhanced by GM-CSF stimulation. Furthermore, cotransfection of Bcl-3 with p52 or p50 in TF-1 cells resulted in significant activation of a c-myb kappa B-TATA-luceriferase reporter plasmid. These findings suggest that Bcl-3 may participate in the transcriptional regulation of certain kappa B-containing genes involved in hematopoiesis, including c-myb.

© 1998 by The American Society of Hematology.


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