Functions of the runt gene family in development

runt 基因家族在发育中的功能

• 批准号: 09044249
• 负责人: SATAKE Masanobu
• 金额: $ 2.94万
• 依托单位: Institute of Development, Aging and Cancer, Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for international Scientific Research
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09044249/
• 关键词: transcription factor; hematopoietic stem cell; acute myeloid leukemia; T lymphocytes; AML1; PEBP2beta; runt; AML1; CBFβ; キメラ遺伝子; 細胞骨格; アポトーシス

The PEBP2 transcription factor functions as a heterodimer composed of the alpha and beta subunits. The alpha subunit is responsible for the DNA binding activity of PEBP2, which is furthermore enhanced by interacting with the beta subunit. The AML1 gene, encoding the alpha subunit of PEBP2, corresponds to the mammalian homologue of Drosophila runt gene, a gene involved in Segmentation, neural development and sex determination in fly. The mammalian PEBP2beta gene encoding the beta subunit of PEBP2 represents a runt-partner gene. Both the AMI.I and PEBP2beta genes are involved in chromosomal rearrangements associated which human acute myeloid leukemia. As a result of translocation and/or inversion, the chimeric genes are generated.The study was carried out to reveal the functions of mammalian runt and runt-partner genes in cell differentiation, transformation and development. The results are summarized as follows.l)The PEBP2 transcription factor is indispensable and functions in a dose dependent manner for the hematopoietic development in the embryonic aorta-gonad-mesonephros region.2)The product of the chimeric gene associate with human AML and involving the PEBP2beta gene impairs the architecture of cytoplasmic cytoskeleton.3)A dose of AML1 transcription factor is critical in deternuning the quality of T cell receptor-mediated signal to cell survival or cell death.

PEBP2 转录因子作为由 α 和 β 亚基组成的异二聚体发挥作用。 α 亚基负责 PEBP2 的 DNA 结合活性，该活性通过与 β 亚基相互作用进一步增强。编码 PEBP2 α 亚基的 AML1 基因对应于果蝇 runt 基因的哺乳动物同源物，该基因参与果蝇的分段、神经发育和性别决定。编码 PEBP2 β 亚基的哺乳动物 PEBP2beta 基因代表矮子伴侣基因。 AMI.I 和 PEBP2beta 基因均参与与人类急性髓系白血病相关的染色体重排。由于易位和/或倒位，产生了嵌合基因。本研究旨在揭示哺乳动物矮基因和矮基因伴侣基因在细胞分化、转化和发育中的功能。结果总结如下：1）PEBP2转录因子对于胚胎主动脉-性腺-中肾区域的造血发育是不可缺少的，并且以剂量依赖性方式发挥作用。2）与人AML相关且涉及PEBP2β基因的嵌合基因的产物损害细胞质细胞骨架的结构。3） AML1 转录因子对于决定 T 细胞受体介导的细胞存活或细胞死亡信号的质量至关重要。

项目成果

Okada,H.,: "AML1(-1-)embryos do not express certain hematopoiesis-related gene transcripts including those of the PU.I gene." Oncogene. 17. 2287-2293 (1998)

Okada,H.,：“AML1(-1-) 胚胎不表达某些造血相关基因转录本，包括 PU.I 基因的转录本。”

Tanaka, Y., Watanabe, T., Chiba, N., Niki, M., Kuroiwa, Y., Nishihira, T., Satomi, S., Ito, Y.and Satake, M.: "The protooncogene product, PEBP2beta/CBFbeta, is mainly located in the cytoplasm and has an affinity with cytoskeletal structures." Oncogene. 15

Tanaka, Y.、Watanabe, T.、Chiba, N.、Niki, M.、Kuroiwa, Y.、Nishihira, T.、Satomi, S.、Ito, Y. 和 Satake, M.：“原癌基因产物，

Chiba, N.: "Differentiation dependent expression and distinct subcellular localization of the protooncogene product, PEBP2β/CBFβ, in muscle development" Oncogene. 14. 2543-2552 (1997)

Chiba, N.：“原癌基因产物 PEBP2β/CBFβ 在肌肉发育中的分化依赖性表达和不同的亚细胞定位”Oncogene，14. 2543-2552 (1997)。

Tanaka, Y.: "The protooncogene product, PEBP2β/CBFβ, is mainly located in the cytoplasm and has an affinity with cytoskeletal structures." Oncogene. 15. 677-683 (1997)

Tanaka, Y.：“原癌基因产物 PEBP2β/CBFβ 主要位于细胞质中，与细胞骨架结构具有亲和力。” 15. 677-683 (1997)。

Chiba, N.: "Differentiation dependent expression and distinct subcellular localization of the protooncogene product, PEBP2β/CBFβ, in muscle development." Oncogene. 14. 2543-2552 (1997)

Chiba, N.：“原癌基因产物 PEBP2β/CBFβ 在肌肉发育中的分化依赖性表达和不同的亚细胞定位。”14. 2543-2552 (1997)