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dc.contributor.authorEzoe, S
dc.contributor.authorMatsumura, I
dc.contributor.authorNakata, S
dc.contributor.authorGale, K
dc.contributor.authorIshihara, K
dc.contributor.authorMinegishi, N
dc.contributor.authorMachii, T
dc.contributor.authorKitamura, T
dc.contributor.authorYamamoto, M
dc.contributor.authorEnver, T
dc.contributor.authorKanakura, Y
dc.identifier.citationBLOOD, 2002, 100 pp. 3512 - 3520
dc.description.abstractGATA-2 is considered to be essential for the development, maintenance, and function of hematopoietic stem cells (HSCs). However, it was also reported that GATA-2 Inhibits the growth of HSCs. To examine the role of GATA-2 in the growth of hematopoietic cells, we introduced an estradiol-inducible form of GATA-2 (GATA-2/estrogen receptor [ER]) into interleukin 3 (IL-3)-dependent cell lines, Ba/F3, 32D, and FDC-P1. Estradiol-induced GATA-2 suppressed c-myc mRNA expression and inhibited IL-3-dependent growth in these clones. As for this mechanism, GATA-2 was found to inhibit ubiquitin/proteasome-dependent degradation of p21(WAF1) and p27(Kip1) and to induce their accumulation by repressing the expression of Skp2 and Cul1, both of which are components of the ubiquitin ligase for p21(WAF1) and p27(Kip1). Overexpression of c-myc restored the expression of Skp2 and Cul1 mRNA, reduced the amounts of p21(WAF1) and p27(Kip1) proteins, and canceled GATA-2-induced growth suppression, suggesting that down-regulation of c-myc expression may be primarily responsible for GATA-2-induced growth suppression. Next, we transduced retrovirus containing GATA-2/ER into murine bone marrow mononuclear cells (MNCs) and stem/progenitor (Sca-1(+)Lin(-)) cells. GATA-2/ER suppressed cytokine-dependent growth of MNCs and Sca-1(+)Lin(-) cells by about 70%, which was also accompanied by the reduced expression of c-myc, Skp2, and Cull mRNA and the accumulation of p21(WAF1) and p27(Kip1) proteins. In addition, the amount of GATA-2 protein was found to decline in hematopoietic stem/progenitor cells that were promoted to enter cell cycle by the stimulation with cytokines. These results suggest that GATA-2 may regulate expression levels of p21(WAF1) and p27(Kip1), thereby contributing to the quiescence of hematopoietic stem/progenitor cells.
dc.format.extent3512 - 3520
dc.titleGATA-2/estrogen receptor chimera regulates cytokine-dependent growth of hematopoietic cells through accumulation of p21(WAF1) and p27(Kip1) proteins
dc.typeJournal Article
rioxxterms.typeJournal Article/Review
pubs.notesaffiliation: Matsumura, I (Reprint Author), Osaka Univ, Grad Sch Med, Dept Hematol & Oncol C9, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan. Osaka Univ, Grad Sch Med, Dept Hematol Oncol & Mol Oncol, Suita, Osaka 5650871, Japan. Univ Tsukuba, Ctr TARA, Tsukuba, Ibaraki, Japan. Univ Tsukuba, Inst Basic Med Inst, Tsukuba, Ibaraki, Japan. Univ Tokyo, Inst Med Sci, Adv Clin Res Ctr, Div Cellular Therapy,Minato Ku, Tokyo, Japan. Inst Canc Res, Chester Beatty Labs, Sect Gene Funct & Regulat, London SW3 6JB, England. keywords-plus: TRANSCRIPTION FACTOR GATA-2; STEM-CELLS; MEGAKARYOCYTIC DIFFERENTIATION; C-MYC; ERYTHROID-DIFFERENTIATION; HUMAN THROMBOPOIETIN; BINDING PROTEIN; GENE-EXPRESSION; SELF-RENEWAL; DNA-BINDING research-areas: Hematology web-of-science-categories: Hematology researcherid-numbers: Yamamoto, Masayuki/A-4873-2010 number-of-cited-references: 53 times-cited: 53 usage-count-last-180-days: 0 usage-count-since-2013: 4 journal-iso: Blood doc-delivery-number: 613YE unique-id: ISI:000179158500012 oa: gold_or_bronze da: 2018-09-17
pubs.notesNot known
pubs.embargo.termsNot known
dc.contributor.icrauthorEnver, Tariqen

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