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代表人类急性髓性白血病基因AML1小鼠同源物的PEBP2αB cDNA的分离。

Isolation of PEBP2 alpha B cDNA representing the mouse homolog of human acute myeloid leukemia gene, AML1.

作者信息

Bae S C, Yamaguchi-Iwai Y, Ogawa E, Maruyama M, Inuzuka M, Kagoshima H, Shigesada K, Satake M, Ito Y

机构信息

Department of Viral Oncology, Kyoto University, Japan.

出版信息

Oncogene. 1993 Mar;8(3):809-14.

PMID:8437866
Abstract

Breakpoints of the t(8;21) chromosome translocation in acute myeloid leukemia are clustered within the human gene, AML1, located on chromosome 21 [Miyoshi, H., Shimizu, K., Maseki, N., Kaneko, Y. & Ohki, M. (1991). Proc. Natl. Acad. Sci. USA, 88, 10431-10434]. The product of AML1 has a region about 130 amino acids long that is highly homologous to the Drosophila segmentation gene runt (runt homology region). The cDNA isolated from mouse fibroblasts encoding the alpha-subunit of polyomavirus enhancer binding protein 2 (PEBP2/PEA2) revealed that it also has a runt homology region (E. Ogawa et al., submitted). In this study, a different cDNA clone presumed to represent the mouse homolog of human AML1 (PEBP2 alpha B) was isolated from a cDNA library derived from B cells. The deduced amino acid sequence of PEBP2 alpha B is 99% identical to that of AML1 for the first 241 residues, including the runt homology region, though their sequences diverge thereafter. On the other hand, PEBP2 alpha B and PEBP2 alpha share only 92% and 82% homologies at the amino acid and nucleotide levels respectively, even for the runt homology region, indicating that these proteins are encoded by distinct genes. While PEBP2 alpha is highly expressed in T-cell lines but not in most of the B-cell lines and functions as an activator of T-cell-specific genes, PEBP2 alpha B is expressed in both types of cells. A possible functional relationship between PEBP2 alpha and PEBP2 alpha B is discussed in relation to leukemogenic potential of AML1.

摘要

急性髓性白血病中t(8;21)染色体易位的断点聚集在位于21号染色体上的人类基因AML1内[三好博之、清水健、増関直、金子洋、大木守(1991年)。《美国国家科学院院刊》,88卷,10431 - 10434页]。AML1的产物有一个约130个氨基酸长的区域,与果蝇分节基因runt(runt同源区域)高度同源。从小鼠成纤维细胞中分离出的编码多瘤病毒增强子结合蛋白2(PEBP2/PEA2)α亚基的cDNA显示它也有一个runt同源区域(小川英树等人,已投稿)。在本研究中,从B细胞来源的cDNA文库中分离出一个不同的cDNA克隆,推测它代表人类AML1的小鼠同源物(PEBP2αB)。PEBP2αB推导的氨基酸序列在前241个残基,包括runt同源区域,与AML1的序列有99%的同一性,不过此后它们的序列出现分歧。另一方面,即使对于runt同源区域,PEBP2αB与PEBP2α在氨基酸和核苷酸水平上分别仅共享92%和82%的同源性,这表明这些蛋白质由不同的基因编码。虽然PEBP2α在T细胞系中高表达,但在大多数B细胞系中不表达,并且作为T细胞特异性基因的激活剂发挥作用,而PEBP2αB在两种类型的细胞中均有表达。本文结合AML1的白血病发生潜能讨论了PEBP2α与PEBP2αB之间可能的功能关系。

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