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Ets蛋白TEL在人类白血病中导致ABL酪氨酸激酶的寡聚化。

Oligomerization of the ABL tyrosine kinase by the Ets protein TEL in human leukemia.

作者信息

Golub T R, Goga A, Barker G F, Afar D E, McLaughlin J, Bohlander S K, Rowley J D, Witte O N, Gilliland D G

机构信息

Division of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.

出版信息

Mol Cell Biol. 1996 Aug;16(8):4107-16. doi: 10.1128/MCB.16.8.4107.

DOI:10.1128/MCB.16.8.4107
PMID:8754809
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC231407/
Abstract

TEL is a member of the Ets family of transcription factors which are frequently rearranged in human leukemia. The mechanism of TEL-mediated transformation, however, is unknown. We report the cloning and characterization of a chromosomal translocation associated with acute myeloid leukemia which fuses TEL to the ABL tyrosine kinase. The TEL-ABL fusion confers growth factor-independent growth to the marine hematopoietic cell line Ba/F3 and transforms Rat-1 fibroblasts and primary murine bone marrow cells. TEL-ABL is constitutively tyrosine phosphorylated and localizes to the cytoskeleton. A TEL-ABL mutant containing an ABL kinase-inactivating mutation is not constitutively phosphorylated and is nontransforming but retains cytoskeletal localization. However, constitutive phosphorylation, cytoskeletal localization, and transformation are all dependent upon a highly conserved region of TEL termed the helix-loop-helix (HLH) domain. TEL-ABL formed HLH-dependent homo-oligomers in vitro, a process critical for tyrosine kinase activation. These experiments suggest that oligomerization of TEL-ABL mediated by the TEL HLH domain is required for tyrosine kinase activation, cytoskeletal localization, and transformation. These data also suggest that oligomerization of Ets proteins through the highly conserved HLH domain may represent a previously unrecognized phenomenon.

摘要

TEL是转录因子Ets家族的成员，在人类白血病中经常发生重排。然而，TEL介导的转化机制尚不清楚。我们报道了一种与急性髓性白血病相关的染色体易位的克隆和特征，该易位将TEL与ABL酪氨酸激酶融合。TEL-ABL融合赋予海洋造血细胞系Ba/F3不依赖生长因子的生长能力，并转化大鼠-1成纤维细胞和原代小鼠骨髓细胞。TEL-ABL持续酪氨酸磷酸化并定位于细胞骨架。含有ABL激酶失活突变的TEL-ABL突变体不持续磷酸化且无转化能力，但保留细胞骨架定位。然而，持续磷酸化、细胞骨架定位和转化都依赖于TEL的一个高度保守区域，称为螺旋-环-螺旋（HLH）结构域。TEL-ABL在体外形成依赖HLH的同源寡聚体，这是酪氨酸激酶激活的关键过程。这些实验表明，TEL HLH结构域介导的TEL-ABL寡聚化是酪氨酸激酶激活、细胞骨架定位和转化所必需的。这些数据还表明，通过高度保守的HLH结构域进行的Ets蛋白寡聚化可能代表了一种以前未被认识的现象。

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本文引用的文献

1
An actin-binding function contributes to transformation by the Bcr-Abl oncoprotein of Philadelphia chromosome-positive human leukemias.肌动蛋白结合功能有助于费城染色体阳性人类白血病的Bcr-Abl癌蛋白介导的细胞转化。
EMBO J. 1993 Apr;12(4):1533-46. doi: 10.1002/j.1460-2075.1993.tb05797.x.
2
SH1 domain autophosphorylation of P210 BCR/ABL is required for transformation but not growth factor independence.P210 BCR/ABL的SH1结构域自身磷酸化是细胞转化所必需的，但并非生长因子非依赖性所必需。
Mol Cell Biol. 1993 Mar;13(3):1728-36. doi: 10.1128/mcb.13.3.1728-1736.1993.
3
The Ets family of transcription factors.Ets转录因子家族。
Eur J Biochem. 1993 Jan 15;211(1-2):7-18. doi: 10.1007/978-3-642-78757-7_2.
4
Dimerization mediated through a leucine zipper activates the oncogenic potential of the met receptor tyrosine kinase.通过亮氨酸拉链介导的二聚化激活了间质表皮转化因子受体酪氨酸激酶的致癌潜能。
Mol Cell Biol. 1993 Nov;13(11):6711-22. doi: 10.1128/mcb.13.11.6711-6722.1993.
5
Acute leukemias of different lineages have similar MLL gene fusions encoding related chimeric proteins resulting from chromosomal translocation.不同谱系的急性白血病具有相似的MLL基因融合，这些融合是由染色体易位产生的，编码相关的嵌合蛋白。
Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8538-42. doi: 10.1073/pnas.90.18.8538.
6
Fusion between transcription factor CBF beta/PEBP2 beta and a myosin heavy chain in acute myeloid leukemia.急性髓系白血病中转录因子CBFβ/PEBP2β与肌球蛋白重链之间的融合
Science. 1993 Aug 20;261(5124):1041-4. doi: 10.1126/science.8351518.
7
Analysis of the DNA-binding and transcriptional activation functions of human Fli-1 protein.人Fli-1蛋白的DNA结合及转录激活功能分析
Oncogene. 1993 Aug;8(8):2167-73.
8
Oncogenic activation of c-ABL by mutation within its last exon.c-ABL通过其最后一个外显子内的突变发生致癌激活。
Mol Cell Biol. 1993 Aug;13(8):4967-75. doi: 10.1128/mcb.13.8.4967-4975.1993.
9
The COOH terminus of the c-Abl tyrosine kinase contains distinct F- and G-actin binding domains with bundling activity.c-Abl酪氨酸激酶的COOH末端包含具有成束活性的不同的F-肌动蛋白和G-肌动蛋白结合结构域。
J Cell Biol. 1994 Feb;124(3):325-40. doi: 10.1083/jcb.124.3.325.
10
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Mol Cell Biol. 1993 Dec;13(12):7587-95. doi: 10.1128/mcb.13.12.7587-7595.1993.