2004 Fiscal Year Final Research Report Summary
Signal transduction in cell division
| Project/Area Number |
15570154
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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 |
Cell biology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
SHIRAKATA Masaki Tokyo Medical and Dental University, Medical Research Institute, Research assistant, 難治疾患研究所, 助手 (70251551)
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| Co-Investigator(Kenkyū-buntansha) |
YAMANASHI Yuji Tokyo Medical and Dental University, Medical Research Institute, Professor, 難治疾患研究所, 教授 (40202387)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Cell cycle reguration / Cell growth / Cancer / Apoptosis |
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| Research Abstract |
Dok-1 and Dok-2 are rasGAP-associated adaptor proteins expressed preferentially in hematopoietic cells. We found that Dok-1 plays an important role of cell cycle progression in cultured cells. We also generated mice lacking Dok-1 and/or Dok-2 ; among them, the double-deficient mice succumbed to myeloproliferative disease resembling human chronic myelogenous leukemia (CML) and chronic myelomonocytic leukemia. The double-deficient mice had increased hematpoietic stem cells and displayed medullary and extramedullary hyperplasia of granulocyte/macrophage progenitors with leukemic potential, and their myeloid cells showed hyper-proliferation and hypo-apoptosis together with enhanced Erk and Akt activation upon cytokine stimulation. Moreover, loss of Dok-1 and/or Dok-2 induced blastic transformation of chronic phase CML-like disease in mice carrying bcr-ab1 gene. These findings demonstrate that Dok-1 and Dok-2 are key negative regulators of cytokine responses and are essential for myeloid homeostasis and suppression of leukemia.
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[Journal Article] Role of Dok-1 and Dok-2 in myeloid homeostasis and suppression of leukemia.2004
Author(s)
Tomoharu Yasuda, Masaki Shirakata, Atsushi Iwama, Asuka Ishii, Yasuhiro Ebihara, Mitsujiro Osawa, Kazuho Honda, Hisaaki Shinohara, Katsuko Sudo, Kohichiro Tsuji, Hiromitsu Nakauchi, Yoichiro Iwakura, Hisamaru Hirai, Hideaki Oda, Tadashi Yamamoto, Yuji Yamanashi
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Journal Title
Journal of Experimental Medicine 200
Pages: 1681-1687
Description
「研究成果報告書概要(欧文)」より
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