2013 Fiscal Year Final Research Report
Analysis of leukemogenesis caused by disordered transcription regulation
| Project/Area Number |
24659456
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | Tohoku University |
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Principal Investigator |
SHIMIZU Ritsuko 東北大学, 医学(系)研究科(研究院), 教授 (40226262)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Keywords | GATA転写因子 / 遺伝子改変マウス / 白血病 / 巨核球 |
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| Research Abstract |
GATA1 is a transcription factor essential for erythroid/megakaryocytic cell differentiation. Acquired mutations deleting the N-terminal region of GATA1 protein are frequently found in acute megakaryoblastic leukemia (AMKL) and transient myeloproliferative disorder (TMD) in children with Down syndrome. We found that full length of GATA1 could restrict proliferation of megakaryocyte progenitors derived from livers of GATA1-null fetus and cell line originally established from AMKL patients, whereas mutant GATA1s lacking consensus motif essential for the interaction sites with Rb protein could not support the GATA1 function on the growth regulation of immature megakaryocytes. This finding indicates that the GATA1 function supported by interaction with Rb protein is involved in the onset of TMD.
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[Journal Article] PGC-1 Coactivator Activity is Required for Murine Erythropoiesis2014
Author(s)
Cui S, Tanabe O, Lim K-C, Xu HE, Zhou XE, Lin JD, Shi L, Shimizu R, Schmidt L, Campbell A, Yamamoto M, Engel JD.
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Journal Title
Mol Cell Biol
Volume: 34(11)
Pages: 1956-1965
DOI
Peer Reviewed
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[Journal Article] Loss of a Rho-regulated actin nucleator, mDia2, impairs cytokinesis during mouse fetal erythropoiesis2013
Author(s)
Watanabe S, De Zan T, Ishizaki T, Yasuda S, Kamijyo H, Yamada D, Aoki T, Kiyonari H, Kaneko H, Shimizu R, Yamamoto M, Goshima G, Narumiya S.
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Journal Title
Cell Report
Volume: 5(4)
Pages: 926-932
DOI
Peer Reviewed
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[Journal Article] GATA factor switching from GATA2 to GATA1 contributes to erythroid differentiation2013
Author(s)
Suzuki M, Koyayashi-Osaki M, Tsutsumi S, Pan X, Ohmori S, Takai J, Moriguchi T, Ohneda O, Ohneda K, Shimizu R, Kanki Y, Kodama T, Aburatani H, Yamamoto M.
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Journal Title
Gene Cells
Volume: 18(11)
Pages: 921-933
DOI
Peer Reviewed
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[Journal Article] Naturally occurring oncogenic GATA1 mutants with internal deletions in transient abnormal myelopoiesis in Down syndrome2013
Author(s)
Toki T, Kanezaki R, Kobayashi E, Kaneko H, Suzuki M, Wang R, Terui K, Kanegane H, Maeda M, Endo M, Mizuochi T, Adachi S, Hayashi Y, Yamamoto M, Shimizu R, Ito E.
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Journal Title
Blood
Volume: 121(16)
Pages: 3181-3184
DOI
Peer Reviewed
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[Journal Article] UG4 enhancer-driven GATA-2 and BMP4 complementation remedies the CAKUT phenotype in Gata2 hypomorphic mutant mice2012
Author(s)
Ainoya K, Moriguchi T, Ohmori S, Souma, T. Takai J, Morita M, Chandler KJ, Mortlock DP, Shimizu R, Lim, KC, Engel JD, Yamamoto M.
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Journal Title
Mol Cell Biol
Volume: 32(12)
Pages: 2312-2322
DOI
Peer Reviewed
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