Analysis of leukemogenesis caused by disordered transcription regulation

转录调控紊乱引起的白血病发生分析

• 批准号: 24659456
• 负责人: SHIMIZU Ritsuko
• 金额: $ 2.41万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24659456/
• 关键词: GATA転写因子; 遺伝子改変マウス; 白血病; 巨核球

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.

GATA1是红细胞/巨核细胞分化必不可少的转录因子。在唐氏综合症儿童中，经常发现删除GATA1蛋白N末端区域的突变和急性巨核细胞白血病（AMKL）和瞬时骨髓增生性疾病（TMD）。我们发现，GATA1的全长可能限制源自AMKL患者最初由AMKL患者建立的GATA1-NULL胎儿和细胞系的巨型核细胞祖细胞的增殖，而缺乏与RB蛋白相互作用的突变GATA1S无法支持GATA1功能的突变gata1s。关于未成熟巨核细胞的生长调节。这一发现表明，与RB蛋白相互作用支持的GATA1函数与TMD的发作有关。

项目成果

ATA2発現低下による単球性白血病の発症メカニズムの解析

ATA2表达降低导致单核细胞白血病发病机制分析

• 作者: 原田伸彦;村田典子;清水律子
• 通讯作者: 清水律子

Loss of a Rho-regulated actin nucleator, mDia2, impairs cytokinesis during mouse fetal erythropoiesis.

• DOI: 10.1016/j.celrep.2013.10.021
• 发表时间: 2013-11
• 期刊: Cell reports
• 影响因子: 8.8
• 作者: Sadanori Watanabe;Tihana De Zan;T. Ishizaki;Shingo Yasuda;H. Kamijo;Daisuke Yamada;T. Aoki;H. Kiyonari;H. Kaneko;R. Shimizu;Masayuki Yamamoto;Gohta Goshima;S. Narumiya

GATA1アミノ末端側亜鉛フィンガーによるDNA結合親和性調節機構が赤血球分化に果たす役割

GATA1氨基末端锌指的DNA结合亲和力调节机制在红细胞分化中的作用

• 发表时间: 2013
• 作者: Mozhgan Khalaj Amirhosseini;Makoto Otsu;Hiromitsu Nakauchi;山本雅之;M. Otsu & J. Ooehara.;Ｌｉ ＳＸ ｅｔ ａｌ．;長谷川敦史,金子寛,山本雅之,清水律子
• 通讯作者: 長谷川敦史,金子寛,山本雅之,清水律子

Epo遺伝子転写調節領域の探索

寻找Epo基因转录调控区

• 发表时间: 2013
• 作者: Ma M.;Ren Q.;Zhang J.C.;Hashimoto K;平野育生,鈴木教郎,峯岸直子,山本雅之,清水律子
• 通讯作者: 平野育生,鈴木教郎,峯岸直子,山本雅之,清水律子

UG4 Enhancer-Driven GATA-2 and Bone Morphogenetic Protein 4 Complementation Remedies the CAKUT Phenotype in Gata2 Hypomorphic Mutant Mice

• DOI: 10.1128/mcb.06699-11
• 发表时间: 2012-06-01
• 期刊: MOLECULAR AND CELLULAR BIOLOGY
• 影响因子: 5.3
• 作者: Ainoya, Keiko;Moriguchi, Takashi;Yamamoto, Masayuki
• 通讯作者: Yamamoto, Masayuki