| Project/Area Number |
14570978
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Osaka University |
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Principal Investigator |
MATSUMURA Itaru Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (00294083)
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| Co-Investigator(Kenkyū-buntansha) |
SHIBAYAMA Hirohiko Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (60346202)
MIZUKI Masao Osaka University, Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (80283761)
KANAKURA Yuzuru Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (20177489)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | GATA-1 / GATA-2 / c-myc / p21WAF1 / p27Kip1 / STAT3 / Ras / Ras / c-Myc / 細胞周期 / 細胞増殖 |
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| Research Abstract |
In this study, we have analyzed the effects of GATA transcription factors on the expression and function of cell cycle regulatory molecules in hematopoietic cells and got the results as follows:
1. A4-HT-inducible from of GATA-2/ERT inhibited the IL-3-dependent growth of BaIF3, 32D, and FDC-P1 cells arid cytokine-dependent growth of normal hematopoletic stem/progenitor cells.
2. GATA-2/ERT suppressed the expression of c-myc and CDK4 mRNA and accumulated p21WAF1 and p27Kip1 proteins, whereas it did not influence the mRNA expression levels of pl6INK4A, p15INK4B, p21WAF1 or p27Kip1.
3. GATA-2 inhibited ubiquitin/proteasome-dependent degradation of p21WAF1 and p27Kip1 and induced their accumulation by repressing the expression of Skp2 and Cull, both of which are components of the ubiquitin ligase for p21WAF1 and p27Kip1.
4. The amount of GATA-2 protein declined in hematopoletic stem/progenitor cells that were promoted to enter cell cycle by the stimulation with cytokines.
5. GATA-1 directly bound to STAT3 and inhibited its DNA-binding activity.
6. GATA-1 inhibited oncogenic Ras (H-RasG12V)-induced MEKK1 activation, thereby suppressed H-RasG12V-dependent growth and survival of Ba/F3 cells.
These results suggest that GATA transcription factors may suppressthe cytokine signaling and modulate the expression of p21WAF1 and p27Kip1, thereby inhibiting cell cycle progression of hematopoietic cells.
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