EDAG regulates the proliferation and differentiation of hematopoietic cells and resists cell apoptosis through the activation of nuclear factor-|[kappa]|B

doi:doi:10.1038/sj.cdd.4401490

Cell Death and Differentiation (2004) 11, 1299–1308. doi:10.1038/sj.cdd.4401490 Published online 27 August 2004

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

Edited by J Cidlowski

C Y Li¹, Y Q Zhan¹, C W Xu¹, W X Xu¹, S Y Wang^1,2, J Lv¹, Y Zhou^1,2, P B Yue¹, B Chen^1,2 and X M Yang¹

¹Beijing Institute of Radiation Medicine, Beijing 100850, PR China
²Department of Pathology of Anhui Medical University, Hefei 230000, PR China

Correspondence: XM Yang, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, PR China. Tel: +86 10 66931424; Fax: +86 10 68212874; E-mail: xmyang2@nic.bmi.ac.cn or xiaomingyang@sina.com

Received 25 March 2004; Revised 18 May 2004; Accepted 16 June 2004; Published online 27 August 2004.

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Abstract

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nuclear factor-kappa B (NF-B), and high DNA-binding activity of NF-B was sustained in Ba/F3 EDAG cells after IL-3 was withdrawn. Inhibition of NF-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-B.

Keywords:

EDAG, NF-B, proliferation, differentiation, apoptosis

Abbreviations:

ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; ANLL, acute nonlymphoblastic leukemia; AS, antisense; ATRA, all trans retinoic acid; CML, chronic myeloid leukemia; EDAG, erythroid differentiation-associated gene; EMSA, electrophoretic mobility shift assay; EPO, erythropoietin; FCS, fetal calf serum; FITC, fluorescein isothiocyanate; IL-2, interleukin-2; IL-3, interleukin-3; MDS, myelodysplastic syndrome; NF-B, nuclear factor-kappa B; PBMCs, peripheral blood mononuclear cells; PBS, phosphate-buffered saline; PHA, phytohemagglutinin; PMA, pentahydroxytiglia myristate acetate; RT-PCR, reverse transcription-polymerase chain reaction