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http://dx.doi.org/10.4110/in.2011.11.6.348

NDRG2 Promotes GATA-1 Expression through Regulation of the JAK2/STAT Pathway in PMA-stimulated U937 Cells  

Kang, Kyeong-Ah (Department of Biological Science and the Research Center for Women's Disease, Sookmyung Women's University)
Jung, Hye-Youn (Department of Biological Science and the Research Center for Women's Disease, Sookmyung Women's University)
Nam, So-Rim (Department of Biological Science and the Research Center for Women's Disease, Sookmyung Women's University)
Lim, Jong-Seok (Department of Biological Science and the Research Center for Women's Disease, Sookmyung Women's University)
Publication Information
IMMUNE NETWORK / v.11, no.6, 2011 , pp. 348-357 More about this Journal
Abstract
Background: N-myc downstream-regulated gene 2 (NDRG2), a member of a newly described family of differentiation-related genes, has been characterized as a regulator of dendritic cells. However, the role of NDRG2 on the expression and activation of transcription factors in blood cells remains poorly understood. In this study, we investigated the effects of NDRG2 overexpression on GATA-1 expression in PMAstimulated U937 cells. Methods: We generated NDRG2-overexpressing U937 cell line (U937-NDRG2) and treated the cells with PMA to investigate the role of NDRG2 on GATA-1 expression. Results: NDRG2 overexpression in U937 cells significantly induced GATA-1 expression in response to PMA stimulation. Interestingly, JAK2/STAT and BMP-4/Smad pathways associated with the induction of GATA-1 were activated in PMA-stimulated U937-NDRG2 cells. We found that the inhibition of JAK2 activation, but not of BMP-4/Smad signaling, can elicit a decrease of PMA-induced GATA-1 expression in U937-NDRG2 cells. Conclusion: The results reveal that NDRG2 promotes the expression of GATA-1 through activation of the JAK2/STAT pathway, but not through the regulation of the BMP-4/Smad pathway in U937 cells. Our findings further suggest that NDRG2 may play a role as a regulator of erythrocyte and megakaryocyte differentiation during hematopoiesis.
Keywords
GATA-1; NDRG2; U937; JAK2/STAT pathway;
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1 Rylski M, Welch JJ, Chen YY, Letting DL, Diehl JA, Chodosh LA, Blobel GA, Weiss MJ: GATA-1-mediated proliferation arrest during erythroid maturation. Mol Cell Biol 23;5031-5042, 2003.   DOI   ScienceOn
2 Heldin CH, Miyazono K, ten Dijke P: TGF-beta signalling from cell membrane to nucleus through SMAD proteins. Nature 390;465-471, 1997.   DOI   ScienceOn
3 Feng XH, Derynck R: Specificity and versatility in tgf-beta signaling through Smads. Annu Rev Cell Dev Biol 21;659- 693, 2005.   DOI   ScienceOn
4 Friend C, Scher W, Holland JG, Sato T: Hemoglobin synthesis in murine virus-induced leukemic cells in vitro: stimulation of erythroid differentiation by dimethyl sulfoxide. Proc Natl Acad Sci U S A 68;378-382, 1971.   DOI
5 Bresnick EH, Lee HY, Fujiwara T, Johnson KD, Keles S: GATA switches as developmental drivers. J Biol Chem 285;31087-31093, 2010.   DOI
6 Fan C, Ouyang P, Timur AA, He P, You SA, Hu Y, Ke T, Driscoll DJ, Chen Q, Wang QK: Novel roles of GATA1 in regulation of angiogenic factor AGGF1 and endothelial cell function. J Biol Chem 284;23331-23343, 2009.   DOI
7 Park Y, Shon SK, Kim A, Kim KI, Yang Y, Cho DH, Lee MS, Lim JS: SOCS1 induced by NDRG2 expression negatively regulates STAT3 activation in breast cancer cells. Biochem Biophys Res Commun 363;361-367, 2007.   DOI   ScienceOn
8 Choi SC, Kim KD, Kim JT, Oh SS, Yoon SY, Song EY, Lee HG, Choe YK, Choi I, Lim JS, Kim JW: NDRG2 is one of novel intrinsic factors for regulation of IL-10 production in human myeloid cell. Biochem Biophys Res Commun 396;684-690, 2010.   DOI   ScienceOn
9 Mitchelmore C, Buchmann-Moller S, Rask L, West MJ, Troncoso JC, Jensen NA: NDRG2: a novel Alzheimer's disease associated protein. Neurobiol Dis 16;48-58, 2004.   DOI   ScienceOn
10 Takahashi K, Yamada M, Ohata H, Honda K, Yamada M: Ndrg2 promotes neurite outgrowth of NGF-differentiated PC12 cells. Neurosci Lett 388;157-162, 2005.   DOI   ScienceOn
11 Lee EB, Kim A, Kang K, Kim H, Lim JS: NDRG2-mediated Modulation of SOCS3 and STAT3 Activity Inhibits IL-10 Production. Immune Netw 10;219-229, 2010.   DOI
12 Carey JO, Posekany KJ, de Vente JE, Pettit GR, Ways DK: Phorbol ester-stimulated phosphorylation of PU.1: association with leukemic cell growth inhibition. Blood 87;4316- 4324, 1996.
13 Ma AC, Fan A, Ward AC, Liongue C, Lewis RS, Cheng SH, Chan PK, Yip SF, Liang R, Leung AY: A novel zebrafish jak2a(V581F) model shared features of human JAK2(V617F) polycythemia vera. Exp Hematol 37;1379-1386, 2009.   DOI   ScienceOn
14 Deng Y, Yao L, Chau L, Ng SS, Peng Y, Liu X, Au WS,Wang J, Li F, Ji S, Han H, Nie X, Li Q, Kung HF, Leung SY, Lin MC: N-Myc downstream-regulated gene 2 (NDRG2) inhibits glioblastoma cell proliferation. Int J Cancer 106; 342-347, 2003.   DOI   ScienceOn
15 Shon SK, Kim A, Kim JY, Kim KI, Yang Y, Lim JS: Bone morphogenetic protein-4 induced by NDRG2 expression inhibits MMP-9 activity in breast cancer cells. Biochem Biophys Res Commun 385;198-203, 2009.   DOI   ScienceOn
16 Cantor AB, Orkin SH: Hematopoietic development: a balancing act. Curr Opin Genet Dev 11;513-519, 2001.   DOI   ScienceOn
17 Arinobu Y, Mizuno S, Chong Y, Shigematsu H, Iino T, Iwasaki H, Graf T, Mayfield R, Chan S, Kastner P, Akashi K: Reciprocal activation of GATA-1 and PU.1 marks initial specification of hematopoietic stem cells into myeloerythroid and myelolymphoid lineages. Cell Stem Cell 1;416-427, 2007.   DOI   ScienceOn
18 Nerlov C, Graf T: PU.1 induces myeloid lineage commitment in multipotent hematopoietic progenitors. Genes Dev 12;2403-2412, 1998.   DOI   ScienceOn
19 Nelsen SM, Christian JL: Site-specific cleavage of BMP4 by furin, PC6, and PC7. J Biol Chem 284;27157-27166, 2009.   DOI
20 Thomas G: Furin at the cutting edge: from protein traffic to embryogenesis and disease. Nat Rev Mol Cell Biol 3;753-766, 2002.   DOI   ScienceOn
21 Cui Y, Jean F, Thomas G, Christian JL: BMP-4 is proteolytically activated by furin and/or PC6 during vertebrate embryonic development. EMBO J 17;4735-4743, 1998.   DOI
22 de Thonel A, Vandekerckhove J, Lanneau D, Selvakumar S, Courtois G, Hazoume A, Brunet M, Maurel S, Hammann A, Ribeil JA, Zermati Y, Gabet AS, Boyes J, Solary E, Hermine O, Garrido C: HSP27 controls GATA-1 protein level during erythroid cell differentiation. Blood 116;85-96, 2010.   DOI   ScienceOn
23 Goldfarb AN: Megakaryocytic programming by a transcriptional regulatory loop: a circle connecting RUNX1, GATA-1, and P-TEFb. J Cell Biochem 107;377-382, 2009.   DOI   ScienceOn
24 Wickrema A, Crispino JD: Erythroid and megakaryocytic transformation. Oncogene 26;6803-6815, 2007.   DOI   ScienceOn
25 Harrison CA, Wiater E, Gray PC, Greenwald J, Choe S, Vale W: Modulation of activin and BMP signaling. Mol Cell Endocrinol 225;19-24, 2004.   DOI
26 Melotte V, Qu X, Ongenaert M, van Criekinge W, de Bru$\ddot{l}$ne AP, Baldwin HS, van Engeland M: The N-myc downstream regulated gene (NDRG) family: diverse functions, multiple applications. FASEB J 24;4153-4166, 2010.   DOI   ScienceOn
27 Choi SC, Kim KD, Kim JT, Kim JW, Yoon DY, Choe YK, Chang YS, Paik SG, Lim JS: Expression and regulation of NDRG2 (N-myc downstream regulated gene 2) during the differentiation of dendritic cells. FEBS Lett 553;413-418, 2003.   DOI   ScienceOn
28 Choi SC, Kim KD, Kim JT, Kim JW, Lee HG, Kim JM, Jang YS, Yoon DY, Kim KI, Yang Y, Cho DH, Lim JS: Expression of human NDRG2 by myeloid dendritic cells inhibits down-regulation of activated leukocyte cell adhesion molecule (ALCAM) and contributes to maintenance of T cell stimulatory activity. J Leukoc Biol 83;89-98, 2008.   DOI
29 He D, Chen T, Yang M, Zhu X, Wang C, Cao X, Cai Z: Small Rab GTPase Rab7b promotes megakaryocytic differentiation by enhancing IL-6 production and STAT3-GATA-1 association. J Mol Med (Berl) 89;137-150, 2011.   DOI   ScienceOn
30 Ma AC, Ward AC, Liang R, Leung AY: The role of jak2a in zebrafish hematopoiesis. Blood 110;1824-1830, 2007.   DOI   ScienceOn
31 Hao J, Daleo MA, Murphy CK, Yu PB, Ho JN, Hu J, Peterson RT, Hatzopoulos AK, Hong CC: Dorsomorphin, a selective small molecule inhibitor of BMP signaling, promotes cardiomyogenesis in embryonic stem cells. PLoS One 3;e2904, 2008.   DOI
32 Adelman CA, Chattopadhyay S, Bieker JJ: The BMP/BMPR/ Smad pathway directs expression of the erythroid-specific EKLF and GATA1 transcription factors during embryoid body differentiation in serum-free media. Development 129;539-549, 2002.
33 Lohmann F, Bieker JJ: Activation of Eklf expression during hematopoiesis by Gata2 and Smad5 prior to erythroid commitment. Development 135;2071-2082, 2008.   DOI   ScienceOn
34 Anderson GJ, Darshan D: Small-molecule dissection of BMP signaling. Nat Chem Biol 4;15-16, 2008.   DOI   ScienceOn
35 Ding YL, Xu CW, Wang ZD, Zhan YQ, Li W, Xu WX, Yu M, Ge CH, Li CY, Yang XM: Over-expression of EDAG in the myeloid cell line 32D: induction of GATA-1 expression and erythroid/megakaryocytic phenotype. J Cell Biochem 110;866-874, 2010.   DOI   ScienceOn
36 Seidah NG: What lies ahead for the proprotein convertases? Ann N Y Acad Sci 1220;149-161, 2011.   DOI   ScienceOn