| Project/Area Number |
18591043
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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 | The University of Tokyo |
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Principal Investigator |
HANGAISHI Akira The University of Tokyo, Faculty of Medicine, Special Lecturer (20344450)
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| Co-Investigator(Kenkyū-buntansha) |
ASAI Takashi The University of Tokyo, Faculty of Medicine, Assistant (10376436)
KUMANO Keiki The University of Tokyo, Faculty of Medicine, Assistant (90396721)
YAMAMOTO Goh The University of Tokyo, Faculty of Medicine, Assistant (70396753)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | tumor suppressor / Blimp-1 / cell cycle / 造血器腫瘍 |
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| Research Abstract |
B lymphocyte-induced maturation protein-1 (Blimp-1) is a transcriptional repressor and is reported to be required for differentiation of many cell lineages. We have previously found that Blimp-1 is located within a common region homozygously deleted in lymphoid malignancies and is mutated in primary lymphoid tumors, suggesting that Blimp-1 has a tumor suppressor role. Here we focus on investigating the effect of Blimp-1 on cell cycle regulation. Exogenous expression of Blimp-1 rapidly induces the expression of p53, p57 and p21, and the cells are arrested at G1/G0 and G2/M phases. Further investigations showed that Blimp-1 induced G1/G0 arrest is dependent on wild type pRb while its effect on G2/M arrest requires functional p53, and as the upstream regulators of pRb, p57 and p21 evoked by Blimp-1 play the cooperative roles on keeping active pRb. A Blimp-1 mutation detected in malignant lymphoma was also found to lose its function in cell cycle arrest. These results suggest that Blimp-1 plays an important role in cell cycle control and therefore the suppression of tumor formation.
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