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[AML1不同转录本对巨噬细胞集落刺激因子受体(M-CSF-R)基因反式激活的影响]

[The effects of different transcripts of AML1 on the transactivation of M-CSF-R gene].

作者信息

Zhang Qing, Wang Min, Xing Hai-yan, Rao Qing, Wang Jian-xiang

机构信息

Institute of Hematology and Blood Diseases Hospital, CAMS and PUMC, Tianjin 300020, China.

出版信息

Zhonghua Xue Ye Xue Za Zhi. 2005 Nov;26(11):641-4.

Abstract

OBJECTIVE

To observe the effects of AML1A and AML1B, two splicing isoforms of AML1, on the transactivation of macrophage colony-stimulating factor receptor (M-CSF-R), and explore the mechanism of hematopoietic stem cell committed differentiation and leukemogenesis.

METHODS

The expressive plasmids of AML1A and AML1B were constructed, and co-transfected into CV-1 cells with a luciferase reporter plasmid containing M-CSF-R promoter. The transactivity of M-CSF-R promoter was assayed by luminometer.

RESULTS

AML1B exhibited a distinct transactivity to M-CSF-R promoter with a sequence-specificity and dosage-dependent manner. AML1A showed no any transactivity but antagonized the effect of AML1B, causing marked reduction of M-CSF-R expression.

CONCLUSION

An intact structure of AML1 is necessary for transactivation of M-CSF-R. AML1A may interfere with the transactivation of AML1B, and play a key role in the fine regulation of committed differentiation of hematopoietic cell.

摘要

目的

观察急性髓系白血病1(AML1)的两种剪接异构体AML1A和AML1B对巨噬细胞集落刺激因子受体(M-CSF-R)反式激活的影响,探讨造血干细胞定向分化及白血病发生的机制。

方法

构建AML1A和AML1B表达质粒,并与含M-CSF-R启动子的荧光素酶报告质粒共转染至CV-1细胞。用发光计检测M-CSF-R启动子的反式活性。

结果

AML1B对M-CSF-R启动子表现出明显的反式活性,呈序列特异性和剂量依赖性。AML1A未表现出任何反式活性,但拮抗AML1B的作用,导致M-CSF-R表达显著降低。

结论

AML1的完整结构是M-CSF-R反式激活所必需的。AML1A可能干扰AML1B的反式激活,并在造血细胞定向分化的精细调节中起关键作用。

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