EDAG regulates the proliferation and differentiation of hematopoietic cells and resists cell apoptosis through the activation of nuclear factor-κB

• DOI: 10.1038/sj.cdd.4401490
• Publication Date: 2004-08-27T09:06:32Z
• Authors: C Y Li; Y Q Zhan; C W Xu; W X Xu; S Y Wang; J Lv; Y Zhou; P B Yue; B Chen; X M Yang
• Keywords: Erythroid Precursor Cells; Transcriptional Activation; 0301 basic medicine; Binding Sites; CD11b Antigen; Cell Survival; NF-kappa B; bcl-X Protein; Nuclear Proteins; Apoptosis; Cell Differentiation; Hematopoietic Stem Cells; Cell Line; Up-Regulation; DNA-Binding Proteins; 03 medical and health sciences; Proto-Oncogene Proteins c-bcl-2; Humans; Interleukin-3; Cell Proliferation; Transcription Factors

Erythroid differentiation-associated gene (EDAG) is considered to be a human hematopoiesis-specific gene. Here, we reported that downregulation of EDAG protein in K562 cells resulted in inhibition of growth and colony formation, and enhancement of sensitivity to erythroid differentiation induced by hemin. Overexpression of EDAG in HL-60 cells significantly blocked the expression of the monocyte/macrophage differentiation marker CD11b after pentahydroxytiglia myristate acetate induction. Moreover, overexpression of EDAG in pro-B Ba/F3 cells prolonged survival and increased the expression of c-Myc, Bcl-2 and Bcl-xL in the absence of interleukin-3 (IL-3). Furthermore, we showed that EDAG enhanced the transcriptional activity of nuclear factor-kappa B (NF-kappa B), and high DNA-binding activity of NF-kappa B was sustained in Ba/F3 EDAG cells after IL-3 was withdrawn. Inhibition of NF-kappa B activity resulted in promoting Ba/F3 EDAG cells death. These results suggest that EDAG regulates the proliferation and differentiation of hematopoietic cells and resists cell apoptosis through the activation of NF-kappa B.