title: NF-kappaB transcription factors are involved in normal erythropoiesis.
abstract: NF-kappaB/Rel designates a widely distributed family of transcription factors involved in immune and acute phase responses. Here, the expression and function of NF-kappaB factors in erythroid proliferation and differentiation were explored. In an erythroleukemia cell line, TF-1, high levels of p105/p50, p100/p52, p65, and IkappaBalpha were detected 24 hours after growth factor deprivation. In response to granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulation, significant induction of p52 expression was observed. GM-CSF also induced nuclear translocation of both p52 and p65. No induction of NF-kappaB factors was observed with erythropoietin stimulation of TF-1 cells. Overexpression of p52 and p65 in TF-1 cells by transient transfection resulted in significant induction of a kappaB-TATA-luciferase reporter plasmid, showing that these factors are functional in vivo in erythroid cells. To determine whether NF-kappaB factors may play a role in normal erythropoiesis, levels of these factors were determined in burst-forming unit-erythroid (BFU-E)-derived cells at different stages of differentiation. The NF-kappaB factors p105/p50, p100/p52, and p65 were highly expressed in early BFU-E-derived precursors, which are rapidly proliferating, and declined during maturation. Furthermore, nuclear levels of NF-kappaB factors p50, p52, and p65 were higher in less mature precursors (day 10 BFU-E-derived cells) compared with more differentiated (day 14) erythroblasts. In nuclear extracts from day 10 BFU-E-derived cells, p50, p52, and p65 were able to form complexes, which bound to kappaB sites in the promoters of both the c-myb and c-myc genes, suggesting that c-myb and c-myc may be among the kappaB-containing genes regulated by NF-kappaB factors in normal erythroid cells. Taken together, these data show that NF-kappaB factors are modulated by GM-CSF and suggest they function to regulate specific kappaB containing genes involved in erythropoiesis.
authors.affiliation: Department of Pediatrics, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, PA 17033-0850, USA.
authors.forename: M Y
authors.initials: MY
authors.lastname: Zhang
authors.forename: S C
authors.initials: SC
authors.lastname: Sun
authors.forename: L
authors.initials: L
authors.lastname: Bell
authors.forename: B A
authors.initials: BA
authors.lastname: Miller
mesh_terms: D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D015672:Erythroid Precursor Cells / Q000187:drug effects / Q000502:physiology; D004920:Erythropoiesis / Q000187:drug effects; D016259:Genes, myc; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D016328:NF-kappa B / Q000096:biosynthesis / Q000502:physiology*; D052002:NF-kappa B p50 Subunit; D011519:Proto-Oncogenes; D051996:Transcription Factor RelA; D014407:Tumor Cells, Cultured
chemical_list: D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D051996:Transcription Factor RelA; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004247:DNA