NF-κB transcription factors are involved in normal erythropoiesis

Min Ying Zhang, Shao Cong Sun, Laurie Bell, Barbara A. Miller

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

NF-κB/Rel designates a widely distributed family of transcription factors involved in immune and acute phase responses. Here, the expression and function of NF-κB factors in erythroid proliferation and differentiation were explored. In an erythroleukemia cell line, TF-1, high levels of p105/p50, p100/p52, p65, and IκBα 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-κB 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 κB-TATA-luciferase reporter plasmid, showing that these factors are functional in vivo in erythroid cells. To determine whether NF-κB 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-κB 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-κB 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 κB sites in the promoters of both the c- myb and c-myc genes, suggesting that c-myb and c-myc may be among the κB- containing genes regulated by NF-κB factors in normal erythroid cells. Taken together, these data show that NF-κB factors are modulated by GM-CSF and suggest they function to regulate specific KB containing genes involved in erythropoiesis.

Original languageEnglish (US)
Pages (from-to)4136-4144
Number of pages9
JournalBlood
Volume91
Issue number11
DOIs
StatePublished - Jun 1 1998

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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